605

0031-6997/4/4304-0605$02.00/0PHARMACOLOGICAL REVIEWS

Copyright © 1991 by The American Society for Pharmacology and Experimental Therapeutics

Index

Vol. 43, No.4Printed in U.S.A.

Pharmacological Reviews

Volume 43

1991

Acetyicholine, mechanism of action of antipsychotics, 588

Action potential, extracellular, NRM 5-HT neuron (fig.), 564Adenocarcinoma, mammary, nitric oxide synthase, 130

Adenosine

agonists and antagonists, cerebellar cGMP (table), 11

modulators, 6receptors for inhibitory agonists, 275

uptake and metabolism, 279

Adenosine 5’-diphosphate

extracellular, metabolism, 255

receptors for stimulatory agonista, 250

Adenylate cyclase

activation, ventricular G proteins, myopathy (table), 218

activation in end-stage 1CM, ventricular G proteins (table), 221

a,-a�noceptor-mediated inhibition (fig.), 492

coupling, beta adrenoceptors, 207

Adenylyl cyclase, inhibition, 486

Adrenal gland, cyclic GMP levels, 124

Adrenaline

-induced positive inotropic effects, left papillary muscles (fig.), 211

-induced stimulation of left ventricular adenylate cyclase, antago-

nism, beta adrenoceptors (fig.), 208

Adrenoceptors

agonists and antagonists (table), 477

alpha

guanine nucleotide regulatory proteins, 490

molecular biology, 500

occupancy and function, 488

proposed interaction (fig.), 493

signal transduction, 500signal transduction mechanisms, 483

structure and function, 475

subclassification, 499

alpha-i

cloning of DNAS, 493competition by agonista and antagonists (table), 495

functional expression, cDNAs, 495

heterogeneity, 477

alpha-2

alignment of amino acid sequences (fig.), 496

cloning of DNAs, 496

DNA expression, 498heterogeneity, 480

occupancy, signal transduction mechanisms, 489

primary structure, kidney (fig.), 497

signal transduction processes, mathematical model (fig.), 491

sodium-hydrogen exchange (fig.), 488

alpha-i and a�pha-2 classification, 476

betaagonists, maximal positive inotropic effects (fig.), 220

agonists, spare receptors in heart, 224

alterations, chronic heart failure, 223

antagonism, stimulation ofleft ventricular adenylate cyclase (fig.),

208

antagonist radioligands (table), 205

antagonists, 228

antagonists, right atria (fig.), 229

density, left ventricle (fig.), 225

effects of drugs, human heart, 228

failing human heart, 216

heart failure (fig.), 217

human heart, 203

left ventricular membranes (fig.), 205

maximal positive inotropic effect, right ventricular trabeculae

(fig.), 227

6 months treatment, metoprolol (fig.), 230

myocardial, subtype distribution (table), 222

nonfailing human heart, 205

positive inotropic drugs, 213

procaterol and noradrenaline (fig.), 229protein phosphorylation, 321

subtype distribution, heart failure (table), 218

subtype distribution, nonfailing human heart (table), 206

transplanted human heart, 226

Afferents, noradrenergic, 13

Ahlner, Johan, Rolf G. G. Andersson, Kristina Torfg#{226}rd, and Krister

L. Axelsson. Organic nitrate esters: Clinical use and mechanisms

of actions, 351

Airway diseases, nitrates, 391

Alcoholism, synapsin variants, 329

Alprazolam, stress and, corticotropin-releasing factor concentrations

(fig.), 455

Alzheimer’s disease

alterations, regional brain corticotropin-releasing factor concentra-

tions and receptors, 460

CRF-like immunoreactivity, receptor binding (fig.), 460

protein phosphorylation, 331

serotonin, 519

studies of m-chlorophenylpiperazine, 532

Amantadine, changes in motor activity, cerebellar cGMP (table), 3

Amino acids

alignment of sequences, alpha-2 adrenoceptors (fig.), 496

branched-chain, 56

branched-chain and aromatic, “false” neurotransmitters, 37

excitatory

GABAergic pathways and, 4

nonselective antagonists, 14

release, 13

-y-Aminobutyric acid

-benzodiazepine receptor complex, 42

-BzR/chloride ionophore supramolecular complex (fig.), 42

excitatory amino acids and, 4

mechanism of action of antipsychotics, 588

receptor complex organization, 41

-y-Aminobutyric acid-A, benzodiazepine receptor modulators, 5

-y-Aminobutyric acid-B, receptor agonista, 6

Ammonia, major contributor, hepatic encephalopathy, 35

Amperozide

pED,o (table), 594

pK1 values (table), 592

606 INDEX

D-Amphetamine, changes in motor activity, cerebellar cGMP (table),

3

fi-Amyloid, precursor protein phosphorylation, neuritic plaques, 333

Analgesia, brain 5-HT, 567

Andersson, Rolf G. G. See Ahlner et al., 351

Anesthetics, barbiturates and, cGMP in the cerebellum, 12

Angina

stable, organic nitrates, 382

unstable, silent myocardial ischemia, myocardial infarction, 387

vasospastic

glyceryl trinitrate, 386isosorbide dinitrate and isosorbide-5-mononitrate, 386

Angiotensin-converting enzyme inhibitors, beta adrenoceptors, 231

Anorexia nervosa, endocrine and cerebrospinal fluid studies, 460

Antibiotics, hepatic encephalopathy, 55

Anticonvulsants, cerebellar cGMP (table), 10

Antidiuretic hormone, disorders (table), 98

Antiemesis, 5-HT3 receptor agents, 582

Antipsychotics

atypical, 588

pED�o (table), 594

pK1 values, 5-HT2 (table), 592

serotonin receptor antagonism, 598

binding properties, serotonin receptors, 592

clinical studies, 599

cortical 5-HT, and striatal pK values (table), 593

effects on serotonin receptors, 587

mechanism of action, neurotransmitters, 588pKd or pK1 values, 5-HT receptors (table), 592

serotonin class 3 receptor antagonism, 598

serotonin-mediated behavior, 597

Anxiety

animal models, 449, 544

depression and, animal models, 537

Anxiety disorder

serotonin function, 516

studies of azapirones, 542

Aorta

effect of dexamethasone, constitutive and inducible nitric oxide

synthase (fig.), 132

time-dependent loss of tone, effect of cycloheximide, L-NIO (fig.),

130

Apomorphine, changes in motor activity, cerebellar cGMP (table), 3

Arachidonic acid, metabolites, vascular actions, organic nitrate esters,

366

L-Arginine

citrulline synthesis, Ca’ dependence, nitric oxide (fig.), 123

platelet aggregation, nitric oxide synthesis (fig.), 121

structural formulae (fig.), 116

Arginine vasopressin

elevated plasma levels, V, antagonists, 96

ethanol-induced gastric lesions (fig.), 87

Arylpiperazines, serotonin-selective, effects in humans, 527

Aspirin, indomethacin and, drug interactions, nitrates, 406

Atenololhuman cardiac beta adrenoceptors (fig.), 213

propranolol and, tachycardia (fig.), 212

Atropine, human cardiac beta adrenoceptors (fig.), 213

Aulakh, C. S. See Murphy et al., 527

Axelsson, Krister L. See Ahlner et a!., 351

Azapironesfood intake, 544

healthy normal subjects, 541

5-HT1A receptors, 541

in vitro and in animals, 543

locomotor activity, 544

neurochemical effects, 543

neuroendocrine measures, 544

patients with neuropsychiatric disorders, 542

Barbiturates, anesthetics and, cGMP in the cerebellum, 12

Basile, Anthony S., E. Anthony Jones, and Phil Skolnick. The patho-

genesis and treatment of hepatic eciphalopathy: Evidence for

the involvement of benzodiazepine receptor ligands, 27

Behavior

anxiety and depression, animal models, 449

corticotropin-releasing factor regulation, laboratory animals, 448

feeding, corticotropin-releasing factor, 449locomoter activation, corticotropin-releasing factor, 448

oral-buccal movements, 573serotonin-mediated, antipsychotic drugs, 597

serotonin-selective arylpiperazines, 527

sexual, corticotropin-releasing factor, 448Benzodiazepine

uganda (fig.), 43nuclei biosynthesis (fig.), 52

Bioassay, vasopressin antagonists, 75

Blood pressure

changes induced by oral administration, L-NAME and L-NMMA

(fig.), 117

DRN 5-HT neuron (fig.), 574

regulation, V1 antagonists, 78

Blood vessels, relaxant effect of glyceryl trinitrate (table), 355

BMY 25801, BRL 24924 and, clinical status (table), 583

Brain

cerebral aqueduct or locus ceruleus, corticotropin-releasing factor

infusion (fig.), 450developmental pharmacology, serotonin, other neurotransmitter, 553

energy metabolism, m-chlorophenylpiperazine, 538

first messengers regulating second messenger generation (table), 303

hypothalamic corticotropin-releasing factor neurons, actions of Cy-

tokines, 444

insulin-induced hypoglycemia, corticotropin-releasing factor mRNA

(fig.), 441

localization, corticotropin-releasmg factor receptors, 433

major corticotropin-releasing factor-stained cell groups, fiber systems

(fig.), 429

nigrostriatal and mesolimbic pathway, serotonergiC innervation, 590

nigrostriatal pathways, serotonergic regulation, dopaminergic func-

tion, 595

pED�, typical atypical antipsychotic drugs (table), 594

phosphoprotein phosphatases, 312

prevention of hyponatremia and cerebral edema, V, antagonists, 88

serine/threonine-specific protein phosphatases (table), 312

serotonergic neurons, behaving animal, 563

specific regions, topical administration, capsaicin, 164water content, serum osmolality, vasopressin antagonist (table), 90

Brodde, Otto-Erich. �- and �9,-adrenoceptors in the human heart:

Properties, function, and alterations in chronic heart failure,

203

Bulimia, migraine and, 532

Buspirone

neuroendocrine responses, 514

single-dose studies in humans, 541

Calcium

antagonists, 230

dependence of nitric oxide and citrulline synthesis, L-arginine, brain

synaptosomal cytosol (fig.), 123

-dependent protein kinases, 306, 308

homeostasis, organic nitrate esters, cyclic GMP, 363-independent nitric oxide synthase (fig.), 129

influx, phosphorylation of GAP-43, 318peak positive left ventricular dP/dT (fig.), 223

-phospholipid-dependent protein kinases, 309

INDEX 607

signal transduction, second messenger systems, 433

sodium chloride and, intracellular accumulation, neurotoxicity, 181

translocation, alpha adrenoceptor signal transduction, 483

Calcium channels, voltage-dependent, 324

Calcium current, capsaicin administration, 176

Capsaicinaction

excitable cells (table), 188neurons, 189

primary afferent neurons, 145

acute and long-term effects, nonmammalian species, 168acute excitatory effects, mammalian sensory neurons, 146

administered to central endings, afferent neurons, 163

administered to peripheral endings, sensory neurons, 164biochemical characterization, recognition site, 174

cell-nonspecific effects, 169

cellular targets, mechanisms of action, selectivity for thin sensoryneurons, 143

differences in sensitivity, mammalian species, 166

interaction with nerve growth factor, 184

intermediate effects, mammalian sensory neurons, 150

intracerebroventricular application, 163

-like substances, 186long-term neurotoxic effects, mammalian sensory neurons, 151mechanisms of action, 170

mechanisms of cell-nonselective effects, 187

ontogenetic shift in neurotoxicity, rat, 186periaxonal administration, 160

pharmacological tool, 189pharmacological tool (table), 190

primary afferent neurons, markers (table), 146resiniferatoxin and, chemical structure (fig.), 145

routes of administration, 190ruthenium red as functional antagonist, 182

selectivity of action, 155, 158, 160

sensitivity, age and strain differences, mammalian species, 167

sensory neurons in culture, 165

sensory neurons in vitro, 165

systemic

adult mammals, 156, 160newborn mammals, 151

targets and selectivity

excitable cells, mammals (table), 148

excitatory action, 147

topical administration, specific brain regions, 164

Capsaicinoids

desensitizing and neurotoxic effects, structure-activity relationships,

171

excitatory effect, structure-activity relationship, 170

Capsozepine, competitive antagonist of capsaicin, 173

Cardiovascular system

corticotropin-releasing factor regulation, autonomic function, other

peripheral actions, 446

inhibition of nitric oxide synthesis, 114regulation, 5-HT neurons, 573

serotonin-selective arylpiperazines, 527

Casein kinase, DARPP-32 cells, 311

Catalepsy, neuroleptic-induced, effect of serotonin, 595

Catecholamines

binding studies, 256false neurotransmitter hypothesis, 39

a-receptor, 255

a-receptor, 284structure-activity relationships, 256

uptake and metabolism, 257

Central nervous system

localization of corticotropin-releasing factor, 428

neuroanatomical relationship, serotonergic and dopaminergic sys-

tems, 589

nitric oxide, 122

Cerebellum

basic circuitry diagram (fig.), 4

cell fractions, 4

cyclic GMP and, motor activity, dopaminergics (table), 3

drug effects on cerebellar cGMP (table), 7

pharmacology of cyclic guanosine 3’,5’-monophosphate, 1

slices, 4

Cerebrospinal fluid

corticotropin-releasing factor concentrations, 458

schizophrenia (fig.), 459

endocrine studies and, anorexia nervosa, 4605-hydroxyindoleacetic acid, 511

Chloride channel, regulation, cystic fibrosis, 329

6-Chloro-2-(l-piperazinyl)pyrazine, studies in humans, 539

m-Chlorophenylpiperazine

food intake, 534

locomotor activity, 536

neuroendocrine measures, 535

other substituted phenylpiperazines and, 529

patients with neuropsychiatric disorders, 530

related piperazines and, in vitro and in animals, 532

temperature, 534

Chlorpromazine, pED�o (table), 594Cholecystokinin peptides, cerebellar cGMP (table), 9

Cholinemodulators, 18

serotonergic interactions, 520

Cholinergics, cerebellar cGMP (table), 8

Circadian rhythm

corticotropin-releasing factor regulation, neuroendocrine function,

435

sleep-wake-arousal cycle, 564Cirrhosis, amelioration of hepatic encephalopathy (fig.), 59

Citrulline, synthesis from L-arginine, Ca’� dependence, nitric oxide

(fig.), 123

Climbing fiber system, cGMP in the cerebellum, 15

Clozapineatypical antipsychotic drugs, 588pED� (table), 594

pK1 values (table), 592

Coccaro, Emil F. See Siever et al., 509Collagen, blood platelet receptors, 271

Convulsants, cerebellar cGMP (table), 10

Coronary vessels, nitrate esters, 380

Corticotropin-releasing factor

administration

gastrointestinal responses, 447

metabolic responses, 447

analgesic and anti-inflammatory properties, 445

autonomic actions (fig.), 446binding in rat olfactory bulb membranes, 433

cerebrospinal fluid concentrations, 458concentrations, alprazolam and stress (fig.), 455

concentrations and receptors, Alzheimer’s disease, 460

-containing neurons and receptors, 428

electrophysiological responses, 451

historical perspectives, 426

hypersecretion, pathophysiology, psychiatric illness, 457

hypophysiotropic system, ontogeny of, 435

infusion, animals in darkened compartment (fig.), 450

-like immunoreactivity, receptor binding, Alzheimer’s disease (fig.),

460

local gonadal actions, 448

localization in peripheral tissues, 430localization of messenger RNA, 432

messenger RNA, insulin-induced hypoglycemia (fig.), 441

608 INDEX

neurons

actions of cytokines, 444

effects of stress, 453extrahypothalamic, miscellaneous changes, 456

extrahypothalamic, pharmacological manipulation, 454

feedback and stress-induced effects, 439

nonhypophysiotropic, pharmacological and environmental pertur-

bation, 453other endocrine functions, 441

responses, miscellaneous manipulations, 442

peptide and messenger RNA localization, 428physiology and pharmacology, 425

pituitary corticotrophs, 436

potentiation of action on corticotroph, 437pressure application, different neurons (fig.), 451

receptors, 433

anterior pituitary, feedback- and stress-induced effects, 441

regulation

autonomic function, other peripheral actions, 446

behavior, laboratory animals, 448immune function, 444

neuroendocrine function, 435

neuron, neurotransmitter regulation, 437

reproductive hormone function, 442

-stained cell groups and fiber systems, rat brain (fig.), 429

stimulation test, 457

Corticotropin-releasing hormone, gene, structural organization, rat

(fig.), 433

Cusack, Noel J. See Hourani and Cusack, 243

Cyclic AMP, contractile force, time course ofeffects, isoprenaline (fig.),

209

Cyclic GMP

action of organic nitrate esters, 357

cerebellarantagonism by drugs (table), 15

drug and behavioral effects, stress, 3

drug effects (table), 7

modulation, NO synthetase inhibitor (table), 14changes in motor activity, dopaminergics (table), 3confounding variables, 2

-dependent protein kinase, 306diagram of basic components (fig.), 357lesions and mutant mice, 2

logit-log dose-response curves, CPP and tiletamine (table), 14

microwave tissue fixation, 2

mouse cerebellar, antagonists, EAA-dependent increases (table), 15

organic nitrate esters, cellular calcium homeostasiS, 363

pharmacology of, cerebellum, 1

relation to mode of action, organic nitrate esters, 359

routes of drug administration, 2

schematic drawing showing cellular mechanisms, mediation, vascular

smooth muscle relaxation (fig.), 365

tissue microdissection, 2

Cycloheximide

dexamethasone and, induction, nitric oxide synthase (fig.), 132

L-NIO and, time-dependent loss of tone, aorta (fig.), 130

Cystic fibrosis, chloride channel regulation, 329

Cytokines, actions on hypothalamic corticotropin-releasing factor neu-rons, 444

Denopamine, beta adrenoceptors, 214

Depressants, cerebellar cGMP (table), 10

Depression

animal models, 449, 544anxiety and, animal models, 537major

corticotropin-releasing factor hypersecretion, 457

signs and symptoms (table), 451

studies of azapirones, 542

studies of m-chlorophenylpiperazine, 531

N-Desmethyldiazepam

diazepam and (fig.), 51

summary of levels (fig.), 53

De Wied, David. See L#{225}zl#{243}et al., 73

Dexamethasone

contitutive and inducible nitric oxide synthases, rat aorta (fig.), 132

cycloheximide and, induction, nitric oxide synthase (fig.), 132

DiazepamN-desmethyldiazepam and (fig.), 51

summary of levels (fig.), 53

Diet, hepatic encephalopathy, 55

Dihydroergotamine, sumatriptan interactions, neurotransmitter recep-

tor (table), 581

DNA

a,-adrenoceptor, 498cloning of a,-adrenoceptor, 493

DNA, complementary

a1-adrenoceptor, functional expression, 495

a�pha-2 adrenoceptor cloning, 496Dobutamine

beta adrenoceptors, 214

left ventricular dP/dT, dilated cardiomyopathy (fig.), 230

peak positive left ventricular dP/dT (fig.), 223

Dopamine

beta adrenoceptors, 214

mechanism of action of antipsychotics, 588-mediated behavior, mesolimbic pathway, effect of serotonin, 597mesolimbic pathways, effect of serotonin, 597

modulators, 16regulation of natriuresis, 330

serotonergic regulation, 595

serotonin and, 520

neuroanatomical relationship, 589

Dopaminergics, changes in motor activity, cerebellar cGMP (table), 3

Dopexamine, beta adrenoceptors, 214Drug discrimination

animal models, anxiety and depression, 544

anxiety and depression, animal models, 537

EAA, -dependent increases, antagonists, mouse cerebellar cGMP levels

(table), 15

EAA agonists, antagonists and, Cerebellar cGMP (table), 11

Edema, cerebral, prevention of hyponatremia, V2 antagonists, 88

Electroencephalography, convulsive studies and, 452

Electrophysiology

m-chlorophenylpiperazine, 533

mesolimbic dopamine pathways, effect of serotonin, 597

responses to corticotropin-releasing factor, 451

serotonergic regulation, dopaminergic function, 595Emesis, 5-HT3 receptor agents, 582

Encephalopathy

hepaticamelioration (fig.), 59

animal models, 34

behavioral characteristics of rabbit (table), 34benzodiazepine ligands, rat brains (fig.), 50benzodiazepine ligands (fig.), 49

benzodiazepine receptor ligands (fig.), 46

benzodiazepine receptor ligands, 48

chronic, 54

clinical manifestations, 29

clinical stages (table), 30

complications of liver disease, 54

definition, 28development of, traditional concepts (fig.), 33

INDEX 609

electrophysiology, 31

GABA/benzodiazepine receptor complex, 42

improvement of hepatocellular function, 54

insufficiency and vascular rearrangement (fig.), 29

metabolites found in abnormal levels (table), 34

neuropathology, 30

pathogenesis and treatment, 27

precipitating factors, 53proposed mechanisms of pathogenesis, 32

reduction, portal-systemic shunting, 54

therapeutic modalities, 53, 54

Endothelial cells, Ca2�-independent nitric oxide synthase, time course

of induction (fig.), 129

Endothelium, interaction with organic nitrate esters, 370

Endothelium-derived relaxing factor

controversy about chemical identity, 112

identification as nitric oxide, 111nitric oxide and, comparison of stability (fig.), 112

Enzyme, activation, capsaicin, 177

Epinine, beta adrenoceptors, 214

Ethanol

cGMP in the cerebellum, 12

corticotropin-releasing factor, actions on HPA axis, 443

-induced gastric lesions, plasma AVP (fig.), 87

Ethylene glycol dinitrate, concentration-effect curve (fig.), 355

Exercise, pharmacokinetics of glyceryl trinitrate, 373

Fatty acids, central nervous system electrical activity, 39

Fenfluramine

neuroendocrine responses, 512

responses, extrahypothalamic corticotropin-releasing factor neurons,

454Fibroblasts, generation of nitric oxide, 130

Flumazenil

antagonist to benzodiazepine, 57efficacy in clinical trials (table), 59

pharmacological properties, 58

potential clinical use, 58remission of chronic intractable PSE (fig.), 60

Fluperlapine

pED� (table), 594

pK1 values (table), 592

Fluphenazine, pED� (table), 594

Fornal, Casimir A. See Jacobs and Fornal, 562

Forskolin, heart rate response to increasing doses, bolus injections

(fig.), 224

GABAergic agents, cerebellar cGMP (table), 9

GAP-43, phosphorylation by Ca2� influx, 318

Gastric circulation

mucosa, V, antagonist (fig.), 86

role of vasopressin, cytoprotection (fig.), 86

vasopressin antagonists, 84

Gastrointestinal system, corticotropin-releasing factor administration,

447

Gene, corticotropin-releasing hormone, structural organization, rat

(fig.), 433

Genetic disorders, role of corticotropin-releasing hormone, animal

models, 443Glucocorticoids, immunologically induced formation, nitric oxide, 131Glucose

DRN 5-HT neuron and cortical EEG (fig.), 572

implication of brain 5-HT, 571

Glyceryl trinitrateabsorption and bioavailability, 374

analysis of, 371

analytic methods for GC determination (table), 372buccal and oral, tolerance development, 393

concentration-effect curve (fig.), 355

Congestive heart failure, 389

distribution, 374handling of samples, 372

influence of posture, 373

influence of sampling site, 372intravenous, tolerance development, 392

invention of, 353

isoprenaline and, induced hypotension, effect of L-NIO (fig.), 119lactate production, ventricular heart muscle (fig.), 363

metabolism and elimination, 375

ointment and patches, 393

oxygen consumption, ventricular heart muscle (fig.), 366

pharmacokinetic data, 374

pharmacokinetics, effect of exercise, 373

pharmacokinetic studies, 370

relaxant effect on blood vessels (table), 355

route of administration, 373

sorption to materials, 370

stable angina pectoris, 382

tolerance development, 392Glycine, NMDA-associated agonists, 13

Glycogen synthase kinase 3, regulation of cell-cell interactions, 311

Gonads, local actions, corticotropin-releasing factor, 448

G-proteins

a-adrenoceptor function, 490

-coupled receptor proteins, schematic model (fig.), 494

-coupled receptors, 321

ventricular

adenylate cyclase activation, myopathy (table), 218adenylate cyclase activation, end-stage 1CM (table), 221

Granisetron

antiemesis, 582clinical status (table), 583

Greengard, Paul. See Walaas and Greengard, 299

Growth hormone, secretion, corticotropin-releasing factor neurons, 441Guanylate cyclase

characteristics of Nervous and Weaver mice (table), 3

proposed scheme for NMDA augmentation (fig.), 21

soluble, trasduction mechanism, nitric oxide, 110

Guinea pig, long-term neurotoxic effects, capsaicin, mammalian sen-

sory neurons, 159

Haloperidol, pED,o (table), 594

Heart

aortic valve disease, 223

atrial tissues, positive inotropic effects, 209

autonomic actions, corticotropin-releasing factor (fig.), 446

biventricular failure, ventricular beta adrenoceptors, subtype distri-

bution (table), 218

chronic failure, alterations, beta adrenoceptors, 223

circulation, vasopressin antagonists, 81

congestive failure, nitrates, 389

dilated cardiomyopathy, dobutamine, left ventricular dP/dT (fig.),

230

end-stage dilated cardiomyopathy, ventricular G proteins (table), 218

end-stage isehemic cardiomyopathy, 220

ventricular G proteins (table), 221

failing, beta adrenoceptors, 216failure, beta adrenoceptors (fig.), 217

human

beta adrenoceptors, 203

effects of drugs, beta adrenoceptors, 228

hypertrophic obstructive cardiomyopathy, 223

idiopathic dilated cardiomyopathy, 217

left ventricle, density, beta adrenoceptors (fig.), 225

left ventricular membranes

antagonism of stimulation, beta adrenoceptors (fig.), 208

610 INDEX

determination, beta adrenoceptors (fig.), 205

mitral valve disease, 221

myocardial beta adrenoceptors, subtype distribution (table), 222nonfailing

beta adrenoceptors, 205numbers of beta adrenoceptors, subtype distribution (table), 206

nonfailing or end-stage DCM, maximal positive inotropic effects,

beta adrenoceptors (fig.), 220peak positive left ventricular dP/dT, dobutamine or calcium gluco-

nate infusion (fig.), 223right atria

beta adrenoceptor antagonists (fig.), 229isoprenaline-induced positive inotropic effect (fig.), 210

procaterol and noradrenaline (fig.), 229spare receptors, beta adrenoceptor agonists, 224

tetralogy of Fallot, 223

transplanted human, beta adrenoceptors, 226Vi antagonist, perfusion pressure changes (fig.), 82

vasoconstriction, vasopressin analogues (fig.), 82

ventricular muscle, lactate production, glyceryl trinitrate (fig.), 363

ventricular tissues, 210

Heart rate

DRN 5-HT neuron (fig.), 574

firing rate of DRN 5-HT neurons (fig.), 570

isoprenaline-induced increases (fig.), 212

response to bolus injections, isoprenaline and forskolin (fig.), 224

Hemodynamics, peripheral, nitrate esters, 378

Heparin, drug interactions, nitrates, 406

Hepatocytes, Kupffer cells and, nitric oxide, 129

Hieble, J. Paul. See Ruffolo et al., 475

Higgs, E. A. See Moncada et al., 109

Histaminemechanism of action of antipsychotics, 588nitric oxide, 124

Holzer, Peter. Capsaicin: Cellular targets, mechanisms of action, andselectivity for thin sensory neurons, 143

Hourani, Susanna M. 0. and Noel J. Cusack. Pharmacological receptorson blood platelets, 243

HP-370, pED,�o (table), 5945-Hydroxyindoleacetic acid

cerebrospinal fluid, 511

patients with affective and personality disorders, 515receptor subtypes, 515

5-Hydroxytryptamine

binding studies and receptor isolation, 259structure-activity relationships, 258

uptake and metabolism, 259Hypertension, DRN 5-HT neuron (fig.), 575

Hypoglycemia, insulin-induced, corticotropin-releasing factor mRNA

(fig.),441

Hyponatremia, cerebral edema and, prevention of, V2 antagonists, 88Hypotension, induced by isoprenaline and GTN, effect of L-NIO (fig.),

119

IC! 204,636, cortical 5-HT, and striatal pK values (table), 593ICS 205-930, antiemesis, 582N-Iminoethyl-L-ornithine

cycloheximide and, time-dependent loss of tone, aorta (fig.), 130hypotension induced by isoprenaline and GTN (fig.), 119platelet anti-aggregatory activity (fig.), 126

Imipramine, binding with platelets, 512Immune function, regulation, corticotropin-releasing factor, 444

Indole, modulators, 19

Insulin

DRN 5-HT neuron and cortical EEG (fig.), 572-induced hypoglycemia, corticotropin-releasing factor mRNA (fig.),

441

Interferon-’y, Ca2�-independent nitric oxide synthase, time course of

induction (fig.), 129

Ion channelsregulation, 322

regulation following intracellular injection, protein kinases, nerve

cells (table), 323

lonophores, GABA/BzR/chloride, supramolecular complex (fig.), 42

Ipsapirone, single-dose studies in humans, 541

Isoprenaline

contractile force and cAMP (fig.), 209GTN and, induced hypotension, effect of L-NIO (fig.), 119

heart rate response to increasing doses, bolus injections (fig.), 224

-induced increases in heart rate (fig.), 212

-induced positive inotropic effect, right atria (fig.), 210-induced stimulation of left ventricular adenylate cyclase, antago-

msm, beta adrenoceptors (fig.), 208

percentage of receptor occupancy, positive inotropic effect (fig.), 226

Isosorbide dinitrate

absorption and bioavailability, 376

distribution, 377isosorbide-5-mononitrate and

congestive heart failure, 389pharmacokinetic data, 376

stable angina pectoris, 384metabolism and elimination, 377

tolerance development, 394isosorbide-5-mononitrate, tolerance development, 394

Jacobs, Barry L. and Casimir A. Fornal. Activity of brain serotonergicneurons in the behaving animal, 562

Jones, E. Anthony. See Basile et al., 27

Kahn, Ren#{233}S. See Siever et a!., 509

Kainate, low-dose response curves, mouse cerebellar cGMP (fig.), 13

Kidney

alpha-2 adrenoceptor, primary structure (fig.), 497

autonomic actions, corticotropin-releasing factor (fig.), 446hemodynamic changes, V, antagonist (fig.), 84

Kupffer cells, hepatocytes and, nitric oxide, 129

Lactuloase, related carbohydrates and, hepatic encephalopathy, 56L#{225}szl#{243},Ferenc, Jr. See IAzl#{243}et al., 73

LIszl#{243},Ferenc A., Ferenc L#{224}sl#{243},Jr., and David De Wied. Pharmacology

and clinical perspectives of vasopressin antagonists, 73

Lawlor, Brian A. See Siever et al., 509

Lawrence, Timothy L. See Siever et al., 509Lergotrile, changes in motor activity, cerebellar cGMP (table), 3

Leech, K. P. See Murphy et al., 527

Ligandsbenzodiazepine

hepatic encephalopathy, rabbits (fig.), 49

hepatic encephalopathy, rat brains (fig.), 50

summary of levels (fig.), 53benzodiazepine receptor

hepatic encephalopathy, 27open field performance, hepatic encephalopathy (fig.), 46

sigma, 14Lipopolysaccharide, Ca2�-independent nitric oxide synthase, time

course of induction (fig.), 129

Liver, nitric oxide synthase activity, lipopolysaccharide (fig.), 131Locomotion

azapirones, 544m-chlorophenylpiperazine, 535

Long-term potentiation, regulation of, 327Loxapine, pED� (table), 594

Macrophages

effect of L-NMMA (fig.), 128synthesis of nitric oxide, 124

INDEX 611

Mammalsadult, systemic capsaicin, 156differences in sensitivity

age and strain differences, 167

capsaicin, 166

newborn, systemic capsaicin, 151, 155, 157MAP-2, phosphorylation, 332

MARCKS protein, phoaphorylation, 317

Mass spectrometry, 15N0 release from porcine aortic endothelial cells

(fig.),114

MDL 72222, clinical status (table), 583Melperone

pEDs4� (table), 594pK1 values (table), 592

Meltzer, Herbert Y. and J. Frank Nash. Effects of antipsychotic drugs

on serotonin receptors, 586

Mental illness, neuropeptide therapy, 4611-(2-Methoxyphenyl)piperazine, studies in humans, 540

N-Methyl-D-aspartate

-associated glycine agonists, 13-associated glycine receptor antagonists, 14

augmentation, proposed scheme (fig.), 21

low-dose response curves, mouse cerebellar cGMP (fig.), 13

Methylphenidate, changes in motor activity, cerebellar cGMP (table),3

Metoprolol, 6 months treatment, beta adrenoceptor density, heart (fig.),

230Mice

characteristics of Nervous and Weaver strains (table), 3

mutant, cyclic GMP, 1Microtubule proteins, phosphorylation, 331

Migrainebulimia and, 532

sumatriptan, 579Moncada, S., R. M. J. Palmer, and E. A. Higgs Nitric oxide: Physiology,

pathophysiology, and pharmacology, 109Monoaminergic agents, cerebellar cGMP (table), 7N-Monomethyl-L-arginine, modulation of cerebellar cGMP, NO syn-

thetase inhibitor (table), 14

NG�Monomethyl.L.arginine

changes in blood pressure (fig.), 117

effect on aortic pressure (fig.), 116

leishmanicidal activity, activated macrophages (fig.), 128

platelet anti-aggregatory activity (fig.), 126

Morphine

response of single NRM 5-HT neuron (fig.), 569tail-flick test, NRM 5-HT neurons (fig.), 567

Mossy fiber system

anatomy/neurochemistry, 16

pharmacology, 16

polysynaptic circuitry (fig.), 17

Murphy, D. L., K. P. Leach, C. S. Aulakh, and T. A. Pigott. Serotonin-

selective arylpiperazines with neuroendocrine, behavioral, tern-perature, and cardiovascular effects in humans, 527

Muscimol, Purkinje neuron responses (fig.), 44

Muscle, smoothsumatriptan effects, 580vascular

cellular mechanisms, cyclic GMP (fig.), 365

cyclic GMP system, organic nitrate esters, 359

hyperpolarization, 366relaxant action, organic nitrate esters (fig.), 370

Myelin basic protein kinase, phosphorylation, 311

Myocardial infarctionglyceryl trinitrate, 388unstable angina, 387

Myocardial isehemia, unstable angina, 387

Myocardium, cyclic GMP system, organic nitrate esters, 359

Nash, J. Frank. See Meltzer and Nash, 586

Natriuresis, dopaminergic regulation, 330

Nemeroff, Charles B. See Owens and Nemeroff, 425

Nerve

alveolar, stimulation, NRM 5-HT neurons (fig.), 569conduction, blockade of, 151

neurogenic inflammation, 581Nerve cells

functional importance, second messenger-regulated protein kinases,

305

regulation of ion channels, intracellular injection, protein kinases

(table), 323Nerve growth factor, interaction with capsaicin, 184Nerve terminal

phosphoproteins, presynaptic receptors, 319

protein phosphorylation, depolarization-induced Ca’� influx (table),

316

Nervous system, function, protein kinases (table), 304

Neuritic plaques, fl-amyloid precursor protein phosphorylation, 333

Neurochemistry, m-chlorophenylpiperazine, 533

Neuroendocrine function, corticotropin-releasing factor regulation, 435

Neuroendocrinology, m-chlorophenylpiperazine, 535Neurofibnillary tangles, tau factor phosphorylation, 332

Neurofilament proteins, phosphorylation, 331Neurons

afferent, central endings, capsaicin administration, 163

capsaicin-sensitive, 169

corticotropin-releasing factor

actions of cytokines, 444distribution, 428

effect of pressure application (fig.), 451

effects of stresa, 453

extrahypothalamic, pharmacological manipulation, 454

feedback and stress-induced effects, 439

nonhypophysiotropic, pharmacological and environmental pertur-

bation, 453

other endocrine functions, 441regulation, 437

responses, miscellaneous manipulations, 442

DRN 5-HT

cortical EEG (fig.), 572

firing rate, heart rate (fig.), 570heart rate and blood pressure (fig.), 574

5-HT1A agonist (fig.), 576hypertension, hypotension (fig.), 575

peak elevation of brain temperature (fig.), 572physiological responses (fig.), 570quiet waking, feeding and active waking (fig.), 576respiratory rate, heating trial (fig.), 571

sleep-wake cycle (fig.), 565

stress, 568

suppression, orientation to opening the door (fig.), 576waking, sleep (fig.), 577

function, protein phosphorylation, 299

5-HT

cardiovascular regulation, 573

mean discharge rates (fig.), 566lack of sensitivity, neurotoxic action, capsaicin, 169

mammalian sensory, acute excitatory effects, capsaicin, 146

NCS 5-HT, transition from REM sleep to wakefulness (fig.), 566

NRM 5-HTalveolar nerve stimulation (fig.), 569

extracellular action potential (fig.), 564mean discharge rate (fig.), 568tail-flick trials (fig.), 567

primary afferent

capsaicin, acute and long-term effects (table), 148

capsaicin actions, 145

612 INDEX

markers, capsaicin sensitivity (table), 146

secondary changes in pathways, 154

sensorycapsaicin, long-term neurotoxic effects, 151

consequences of excitation, 149

culture, capsaicin, 165

intermediate effects, capsaicin, 150

in vitro, effects of capsaicin, 165mechanisms of action, 188

mechanisms of selective effects, 174

peripheral endings, capsaicin administration, 164peripheral endings, capsaicin action, 184

serotonergic, behaving animal, 563

thin sensory, capsaicin, 143Neuropeptides, therapy of human mental illnese, 461

Neuropeptide Y, corticotropin-releasing factor, actions on HPA axis,

443

Neuropsychiatric disorders

overview, 510

serotonin and, 507

serotonin receptor subtypes, 579

studies of azapirones, 542

studies with m-chlorophenylpiperazine, 530

Neurotoxins, synergism, 38, 39Neurotransmitter

developing systems, interactions, 557excitatory amino acid, 40

“false”, branched-chain and aromatic amino acids, 37

interaction, serotonin, 516

liver failure, 39mechanism of action, antipsychotics, 588

pathways, regulation of interactions, 325

regulation of corticotropin-releasing factor, 437

regulation of synthesis, tyrosine hydroxylase, 314

release, synapsins, 314

synthesis and release, phosphoproteins, presynaptic function, 314Neutrophils, nitric oxide, 128

Nichols, Andrew J. See Ruffolo et al., 475

Nitrate esters

coronary vessels, 380in vitro evaluation of effects, 354

in vivo evaluation of effects, different target organs, 378

mode of action, cyclic GMP, 359

organic

arachidonic acid metabolites, 366

chemical structure (fig.), 353

clinical use, mechanisms of actions, 351

cyclic GMP, cellular calcium homeostasis, 363

explanation of tolerance (fig.), 401

interaction with endothelium, 370

mechanism of, 398

other suggested mechanisms, 365pharmacokinetics, 370

proposed mechanism of action, cellular level, 357

relaxant action, vascular smooth muscle (fig.), 370

tissue biotransformation, 367

relaxant effect, regional and species differences, 355

vasodilatory effects, 356

Nitrates

airway diseases, 391

dependency, 404clinical problem, 404

mechanism of, 404

drug interactions, 406miscellaneous therapeutic uses, 391

noncardiovascular uses, 391

organic

clinical therapeutic use, 382cross-tolerance, 397

differences between different target organs, 397

tolerance development and dependency, 392peripheral vascular diseases, 391

relationship between pharmacokinetics, therapaeutic effects, 377side effects, 407

Nitric oxide

Ca2� dependence, citrulline synthesis from L-arginine (fig.), 123

effector molecule, immunological reactions, 124endothelium-derived relaxing factor, 111

immunologically induced formation in vivo, 130

inhibition by glucocorticoids, 131

inhibition of synthesis, cardiovascular system, 114

measured by bioassay and by chemilumineseence, 111

novel inhibitors, 116pathological implications, 118pharmacological actions, 120

pharmacological and physiological implications, 117

physiology, pathophysiology, pharmacology, 109physiology and pathophysiology of synthesis, 126release from porcine aortic endothelial cells, mass spectrometry (fig.),

114

synthesis, 114, 120

L-arginine, platelet aggregation (fig.), 121

macrophages, 124transduction mechanism, soluble guanylate cyclase, 110

Nitric oxide synthase

activity in rat liver, lipopolysaccharide (fig.), 131Ca2�-independent (fig.), 129characteristics, 125constitutive and inducible, effect of dexamethasone, rat aorta (fig.),

132induction, effect of cycloheximide, dexamethasone (fig.), 132

similarities and differences, constitutive and inducible groups (table),

126NG.Nitro.L�arginine methyl ester, changes in blood pressure (fig.), 117

Nitroprusside, chemical structure of organic nitrate esters (fig.), 353

Nociception538

tail-flick test, NRM 5-HTneurons (fig.), 567Noradrenaline

-induced positive inotropic effects, left papillary muscles (fig.), 211

-induced stimulation of left ventricular adenylate cyclase, antago-nism, beta adrenoceptors (fig.), 208

Noradrenergic modulators, cGMP in the cerebellum, 20

Noradrenergic system, function of, 514

Norepinephrine, mechanism of action of antipsychotics, 588

Obsessive-compulsive disorder, studies of m-chlorophenylpiperazine,

530Olfactory bulb, rat membranes, corticotropin-releasing factor binding,

433

Ondansetron, antiemesis, 582Opiates

cerebellar cGMP (table), 8

cGMP in the cerebellum, 19ORG 5222, cortical 5-HT2 and striatal pK1 values (table), 593Owens, Michael J. and Charles B. Nemeroff. Physiology and pharma-

cology of corticotropin-releasing factor, 425

Oxygen consumption, effect of glyceryl tninitrate, ventricular heartmuscle (fig.), 366

Palmer, R. M. J.. See Moncada et al., 109

Panic disorder, studies of m-chlorophenylpiperazine, 530Pentaerythreitol tetranitrate, chemical structure of organic nitrate

esters (fig.), 353Peptide, release, capsaicin, 177

INDEX 613

Peripheral tissues, localization of corticotropin-releasing factor, 430

Perlapine, pK1 values (table), 592Peroutka, Stephen J. Serotonin receptor subtypes and neuropsychiatric

diseases: Focus on 5-HT1D and 5-HT3 receptor agents, 578

Pharmacology, developmental, 553, 558

Phenols, liver enzymes, 39

Phenylpiperazines

m-chlorophenylpiperazine, 529substituted, studies in humans, 539

Phosphatidylinositol, turnover, cyclic nature (fig.), 484

Phosphodiesterase inhibitors, beta adrenoceptors, 231

Phospholipid, metabolism, 484

Phosphoprotein phosphatases, brain, 312

Phosphoproteins

clinical disorders and, 328

nerve terminal, presynaptic receptors, 319

postsynaptic function, 319presynaptic function, 314

Phosphorylase kinase, brain, 309Pigott, T. A. See Murphy et a!., 527

Pipamperone, pK1 values (table), 592Piperazines, m-chlorophenylpiperazine, in vitro and in animals, 532

Piribedil, changes in motor activity, cerebellar cGMP (table), 3

Pitressin, serum sodium level, V, antagonists (fig.), 89

Pituitary

anterior, corticotropin-releasing factor receptor, feedback- and

stress-induced effects, 441localization, corticotropin-releasing factor receptors, 433

Plasma membrane, receptors, regulation, protein phosphorylation (ta-

ble), 320Platelet-activating factor

binding studies and receptor isolation, 269

blood platelet receptors, 267

structure-activity relationships, 268uptake and metabolism, 270

Platelets

aggregation, L-arginine, nitric oxide synthesis (fig.), 121

anti-aggregatory activity, effect of L-NIO, L-NMMA (fig.), 126cyclic GMP system, organic nitrate esters, 359

-imipramine binding, 512in vivo evaluation of effects, nitrate esters, 381pharmacological actions of nitric oxide, 120pharmacological receptors, 243

responses, 245serotonin uptake, 512stimulus-response coupling, 247structure and function, 244

Polyamines, antagonism, effects of NMDA, quisqualate receptor acti-vation, 14

Posture, influence on glyceryl trinitrate, 373

Potassium channelactivation, 366nerve cells, 323

Practolol, propranolol or, salbutamol-induced tachycardia (fig.), 213Prenalterol, beta adrenoceptors, 214Prolactin, secretion, atypical antipsychotic drugs, 588

Pro-opiomelanocortin, corticotropin-releasing factor regulation, neu-roendocrine function, 435

Propranolol

atenolol and, tachycardyia (fig.), 212

practolol or, salbutamol-induced tachycardia (fig.), 213

Prostaglandins

Na�/W exchange, alpha adrenoceptors, platelets (fig.), 488structure-activity relationships, 280

thromboxane and, 262Protein

phosphorylationbrain, first messengers (table), 301

functional importance, 300neuronal, multiple sites (table), 302

neuronal function, 299

systems, 301Protein kinases

activation by second messengers, 303

brain, 302

Ca’�/calmodulin-dependent, 306, 308

Ca’�/phospholipid-dependent, 309

cyclic GMP-dependent, 306cyclic nucleotide-dependent, 303

general mechanisms for activation, 302

nervous system function (table), 304

neurofilament, 311

regulation of ion channels (table), 323

second messenger-independent, 311

second messenger-regulated, 303tyrosine-specific, 311

Protein phosphatasesserine/threonine-specific (table), 312

tyrosine-specific, 313

Protein phosphorylationAlzheimer’s disease, 331

depolarization-induced Ca’� influx, nerve terminals (table), 316regulation of plasma membrane receptors (table), 320

Protooncogenes, tyrosine-specific protein kinases, 311

Psychiatric disorders, role of serotonin, 509

Psychiatric illness, pathophysiology, corticotropin-releasing factor hy-

persecretion, 457Psychiatry, serotonin function, 516

Purkinje neuronsdifferential sensitivity (fig.), 45

responses, rate meter records, muscimol (fig.), 44

responses to Ro 14-7437 (fig.), 45

Pyrogen, activity of DRN-5HT neuron (fig.), 571

Pyruvate dehydrogenase kinase, activation in brain, 311

Quipazine, studies in humans, 540

Quisqualate, low-dose response curves, mouse cerebellar cGMP (fig.),

13

Raclopride, pED,o (table), 594

Radioligands, beta-adrenoceptor antagonist (table), 205

Ratlong-term neurotoxic effects, capsaicin, mammalian sensory neurons,

151, 160

ontogenic shift in neurotoxicity, capsaicin, 186

Receptorsadenosine, agonists and antagonists (fig.), 276

adenosine A2, characteristics, Nervous and Weaver mice (table), 3

adenosine 5’-diphosphate

agonists (fig.), 251

antagonists (fig.), 252

affinity profile

azapirones, 543

second messenger system effects, 532

alpha, catecholamines, 255

benzodiazepine

antagonists, 57

GABA, hepatic encephalopathy, 42

ligands, hepatic encephalopathy, 27, 48

ligands (fig.), 46

modulators, 5

beta, catecholamines, 284

blood platelets, 243cholecystokinin, modulators, 18

corticotropin-releasing factor, 433

anterior pituitary, feedback- and stress-induced effects, 441

614 INDEX

biochemical characterization, 433

CRF-like immunoreactivity (fig.), 460

distribution, 428

localization, 433localization, pituitary and brain, 433signal transduction, second messenger systems, 434

excitatory amino acid, modulators, 12

GABA, organization and function, 41

GABAA, protein phosphorylation, 320GABAB, agonists, 6

G-protein coupled, 321

schematic model (fig.), 494

growth factor, 312

5-HT,

down-regulation, 594pK1 values, atypical psychotics (table), 592

5-HT,, 582agents (table),583

antagonism, antipsychotic drugs, 598a,mputational model (table), 584

5-HT1A, azapirones, 5415-hydroxyindoleacetic acid, subtypes, 515

influence on development, 555intracellular, 322

ion channel-coupled, 319

isolation, binding studies, 5-hydroxytryptamine, 259

muscarinic acetylcholine, 321

neurotransmitter

DHE and sumatriptan interactions (table), 581serotonin, brain development and pharmacology, 553

nicotinic acetylcholine, 319

occupancy, positive inotropic effect, isoprenaline (fig.), 226plasma membrane, regulation, protein phosphorylation (table), 320

platelet-activating factor, agonists and antagonists (fig.), 268

platelet (fig.), 283

platelet (table), 282

presynaptic, nerve terminal phosphoproteins, 319

programmable, 555prostaglandin, agonista (fig.), 281

regulation of function, 319

serotonin, see also 5-HTagonists, neuroendocrine responses, 513

antagonism, atypical antipsychotics, 598

binding properties of antipsychotics, 592effects, antipsychotic drugs, 587

“families”, 590physiological effects, 543

subtypes, 591

subtypes, neuropsychiatric diseases, 579

subtypes, physiological effects, 534spare, beta adrenoceptor agonists, heart, 224

stimulatory agonists, adenosine 5’-diphosphate, 250

target tissues, 556

thromboxane A2, agonists and antagonists (fig.), 263

tyrosine kinase-coupled, 322vasopressin, subtypes, antagonists, 92

Renzapride, antiemesis, 582Reproductive hormone, function, corticotropin-releasing factor, 442

Reserpine, corticotropin-releasing factor, actions on HPA axis, 443

Resiniferatoxin

capsaicin and, chemical structure (fig.), 145

potent capsaicin agonist, 171

Respiration

activity of DRN 5-HT neurons (fig.), 571depression, cGMP levels, 3

Rilapine, pK1 values (table), 592

Risperidone

cortical 5-HT, and striatal pK1 values (table), 593pED�,o (table), 594

RMI-81582, pK1 values (table), 592

RNA, messengercorticotropin-releasing factor peptide, 428corticotroptin-releasing factor, insulin-induced hypoglycemia (fig.),

441localization of corticotropin-releasing factor, 432

RO 363, beta adrenoceptors, 214

Ro 14-7437, Purkinje neuron responses (fig.), 45

Ruffolo, Robert R., Jr., Andrew J. Nichols, Jeffrey M. Stadel, and J.Paul Hieble. Structure and function of a-adrenoceptors, 475

Ruthenium red, functional antagonist of capsaicin, 182

SCH 23390, pK1 values (table), 592

Schizophrenia

cerebrospinal fluid CRY-like immunoreactivity (fig.), 459mechanism of action of antipsychotics, 588serotonin, 519

studies of m-chlorophenylpiperazine, 531Serine

protein phosphatases, 312protein phosphatases in brain (table), 312

Serotonin

Alzheimer’s disease, 519

cholinergic interactions, 520

dopamine and, 520

neuroanatomical relationship, 589

false neurotransmitter hypothesis, 39

feedback control, 575function

affective and personality disorders, 511

other psychiatric disorders, 516glucoregulation, 571

innervation, nigrostriatal and mesolimbic pathways, 590

mechanism of action of antipsychotics, 588-mediated behaviors, antipsychotic drugs, 597

mesolimbic dopaniine pathways, 597

neuroleptic-induced catalepsy, 595

neuron, extracellular action potential (fig.), 564

neuropsychiatric disorders and, 507

neurotransmitter interaction, 516

other neurotransmitter receptors and, brain development, develop-

mental pharmacology, 553

overview of neuropsychiatric disorders, 510pharmacological implications, 521

physiological regulation, 569

postsynaptic receptor responsiveness, 515

precursors, neuroendocrine responses, 512

regulation of dopaminergic function, 595

role in psychiatric disorders, 509schizophrenia, 519-selective arylpiperazines, effects in humans, 527

uptake in platelets, 512Serotonin receptor agonists, neuroendocrine responses, 513Sertindole, cortical 5-HT2 and striated pK1 values (table), 593Setoperone, pK1 values (table), 592Sexual function, m-chlorophenylpiperazine, 538

Shunt, portal-systemic, reduction, hepatic encephalopathy, 54

Siever, Larry J., Ren#{233}S. Kahn, Brian A. Lawlor, Robert L. Trestman,

Timothy L. Lawrence, and Emil F. Coccaro. Critical issues in

defining the role of serotonin in psychiatric disorders, 509Skolnick, P. See Basile et al., 27Sleep

m-chlorophenylpiperazine, 538

REM, wakefulness transition, NCS 5-HT neuron (fig.), 566-wake-arousal continuum, 5-HT neurons (fig.), 566-wake-arousal cycle, 564

INDEX 615

excretion

Zacopride, clinical status (table), 583

Zotepine, pK1 values (table), 592

-wake cycle, DRN 5-HT neuron (fig.), 565

SM-9018, cortical 5-HT, and striated pK1 values (table), 593

Sodium, -hydrogen exchange, 487

transduction, a2-adrenoceptors and platelets (fig.), 488Sodium channels, voltage-sensitive, 323Sodium chloride, calcium and, intracellular accumulation, neurotoxic-

ity, 181Stadel, Jeffrey M. See Ruffolo et al., 475

Stressalprazolam and, corticotropin-releasing factor concentrations (fig.),

455brain 5-HT, 568

corticotropin-releasing factor neurons, 453

drug and behavioral effects, cerebellar cGMP, 3

secondary effects, 453

Suicide, controls and, composite Scatchard analysis, frontal cortical

sample (fig.), 460Sulfliydryl, replenishment, tolerance, organic nitrates, 402

Sumatriptanbiochemical and neurochemical effects, 581

clinical efficacy (table), 580clinical studies, 579

DHE and, neurotransmitter receptor (table), 581

history of (table), 579pharmacology of, 580side effect profile (table), 580

Synapsins

regulation of neurotransmitter release, 314

variants and alcoholism, 329

Tachycardia

atenolol and propranolol (fig.), 212salbutamol-induced, practolol or propranolol (fig.), 213

Tau factor

microtubule function, 332phosphorylation, neurofibrillary tangles, 332

Temperature

brain, DRN 5-HT neuron (fig.), 572

m-chlorophenylpiperazine, 534physiological effects, serotomn receptors, 543serotonin-selective arylpiperazines, 527

Tenilapine, pK1 values (table), 592

1,2,3,4-Tetranitratobutan, concentration-effect curve (fig.), 355

Thermoregulation, brain 5-HT, 570

Thioridazine, pED�,o (table), 594

Threitol tetranitrate, concentration-effect curve (fig.), 355

Threonine, -specific protein phosphatases, 312

brain (table),312

Thrombin, blood platelet receptors, 271

Thromboxane, prostaglandins and, 262

Thromboxane A,, Na�/W exchange, alpha adrenoceptors, platelets

(fig.), 488

Thyrotropin-releasing hormone, analogues, 18Tiospirone

pED�o (table), 594pK1 values (table), 592

Torfg#{226}rd,Kristina. See Ahlner et al., 351Trestman, RObert L. See Siever et a!., 509TRH peptides, cerebellar cGMP (table), 9Trinitro toluene, chemical structure of organic nitrate esters (fig.), 353

Tryptophan, plasma, 511

Tubulin, phosphorylation by cAMP-dependent protein kinase, 332

Tyrosine, -specific protein phosphatases, 313

Tyrosine hydroxylase, regulation of neurotransrnitter synthesis, 314

Urine

osmolality, pitressin (fig.), 89

V, antagonist (fig.), 88

vasopressin antagonists (fig.), 87

Vasculature, nitric oxide, 110, 129

Vasodilationinduced by nitrate esters, 354

nitrate esters, 356

Vasodilators, other antianginal drugs and, drug interactions, nitrates,

407

Vasopressin

antagonists

antidiuretic responses (table), 77

antidiuretic responses, 76

bioassay, definition of antagonist potency, 75

central and peripheral circulation, 78

change in urine excretion (fig.), 87

chemical structure and biological activity, 75

chemical structure of d(CH,),Tyr(Me)AVP (fig.), 77

chemical structure of V, antagonists (fig.), 77

elevated plasma arginine-vasopressin levels, 96

pharmacology and clinical perspectives, 73

physiological and pathophysiological roles, 78

potency, 76

pressor responses, 76

release, adrenocorticotrophic hormone, 90

serum osmolality, water content of brain (table), 90

serum sodium level, pitressin (fig.), 89

sodium excretion (fig.), 89

synthesis, 75

therapeutic effects, 97

treatment, clinical significance, 95

urine excretion and osmolality, pitressin (fig.), 89

urine excretion (fig.), 88

V2 and V, antagonists with opening rings (fig.), 79

vasopressor responses (table), 77

water metabolism, 86

binding studies and receptor isolation, 261

structure-activity relationships, 261

Visual-evoked response

abnormalities (fig.), 43

GABA/benzodiazepine receptor complex, 42

Walaas, Sven Ivar and Paul Greengard. Protein phosphorylation and

Water

neuronal function, 299

content of brain, serum osmolality, vasopressin antagonist (table),

90

metabolism, role, V2 antagonists, 86

Whit.aker-Azmitia, Patricia M. Role of serotonin and other neurotrans-

mitter receptors in brain development: Basis for developmental

pharmacology, 553

Wilker, Jeffrey C. and Wilmot, Carole A. Serotonin and neuropsychi-

atric disorders, 507

Wilmot, Carole A. See Wilker et a!., 507

Wood, Paul L. Pharmacology ofthe second messenger, cyclic guanosine

3’,5’-monophosphate, in the cerebellum, 1

Xamoterol, beta adrenoceptors, 214

Yohimbine, binding, competition by agonists and antagonists (table),

498