CNS stimulant

Used in treatment of depression and as analeptics.

I. Analeptics

Drugs enhance the response to sensory stimulation

Respiratory stimulant

1 .Nikethimide

Et

Et

N

N

O

2 .Ethamivan

OCH3

C2H5

C2H5N

O

OH

3 .Methylxanthines

Caffeine Theophylline Theobromine

N

NN

NO

R1

O R3

R2

II. Antidepressants

MAO inhibitors TCAs Miscellaneous

A. MAO Inhibitors Elevate biogenic amine by inhibiting MAO.

hydrazine Non hydrazine

Iproniazide Tranycyprominephenelzine

1. Iproniazide

S.E

N

NHONH

CH3

CH3

Hydrazine derivative

2. phenelzine

NH

NH2

Non hydrazine derivatives

Less SE

Tranylcypromine

NH2

B. Tricyclic antidepressants (TCAs)

SAR Side effects

anticholinergic effects

N

N

R

R

1. Imipramine hydrochloride (tofranil)

Close relative to antipsychotic phenothiazines SE: anticholinergic and sedative efffects

(CH2)3 N

N

CH3

CH3

2 .Desipramine hydrochloride

(CH2)3 NH

N

CH3

.HCl

3 .Amitriptyline hydrochloride

NCH3

CH3

.HCl

4 .Nortriptyline

5. Doxepin hydrochloride

Oxacongener.

O

N

CH3

CH3

.HCl

C. Miscellaneous

Effects on cardiovascular system.

NH

CH3

1 .Maprotiline hydrochloride

2.Trazodone hydrochloride

Similar to fluorobutyrophenone 5HT SE: sedation

NN

N N

N

O

Cl

3. Fluoxetine

Serotonin reuptake inhibitor

F3C

NHCH3O

III. psychadelics

Local anesthesia

Characteristics for an ideal local anaesthetics

- reversible blockade of sensory nerve fibers with a minimal effect on the motor nerve activation

Toxicity and side effects Effects on excitable membranes such as in the

heart, the neuromuscular junctions, and the CNS. With more effect on neuromuscular junctions and the CNS.

convulsions, followed by severe CNS depression, (particularly of the respiratory and cardiovascular centers). Due to inhibtion of inhibtory neurons as GABA system.

amide-type local anesthetics likely to produce CNS side effects than the ester- type compounds

SE depend on route and site of administration, the lipid solubility and metabolic stability of local anesthetics.

allergic reactions rare

More with p-amino-benzoic ester-type amide- type: antiarhythmic (parenterally and at

a subanesthetic dosage) effect on Na channel.

SAR Lipophilic portion

NH2

C O CH2 CH3

O

H2N+

C O CH2 CH3

O -

Intermediate chain

- Short alkyl (1-3) carbons- Nature of chain determine stability and

duration (amide more resistant)- Branching increase the duration

• hydrophilic portion

Tertiary alkyl amine form water soluble

Classification

Ester type Amide type

Ester type procaine

NH2

ON(C2H5)2

O

Procaine

• benzocaine

NH2

O

O CH2CH3

Benzocaine

• Tetracaine

C4H9 NH

ON(C2H5)2

O

Tetracaine

• benoxinate

C4H9

NH2

ON(C2H5)2

O

O

Benoxinate

Amide type Lidocaine

CH3

CH3

NH

N(C2H5)2

O

Lidocaine

CH3

CH3

NH

O

NCH3

Mepvacaine

Synthesis of lidocaine

CH3

CH3

NH2

+Cl

ClO

CH3

CH3

NHCl

O

NH

CH3

CH3

Lidocaine

Metabolism

Ester type esterase interaction with anticholinesterase increase toxicity

Antagonize the antibacterial activity of sulfonamide

Amide type: