hypnotics screening methods by tarun biswas
DESCRIPTION
Seminar M.Pharm Sem 2ndTRANSCRIPT
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Guided By Mr.Rupesh GautamSr.Lecturer in Pharmacology
Jaipur College of PharmacyRajasthan, India
Hypnotics Screening MethodsBy Tarun BiswasM.Pharm Sem.IIDept. of Pharmacology
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• Hypnotic:- Hypnotic drug are that which induce and / or maintain sleep, similar to normal arousable sleep.
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Screening Methods
1. Potentiation of hexobarbital sleeping time
2. Experimental insomnia in rats3. EEG registration in conscious cats4. Automated rat sleep analysis
system
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1.Pontentiation of hexobarbital sleeping timeprinciple:-. The test is used to elucidate CNS activity
of drugs . Not only hypnotics, sedative,
tranquilizers but also antidepressants . The loss of righting reflex is measured
for the duration of hexobarbital sleeping time
. Mice are used in this test.
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Procedure cont ….
• NMRI mice(male) in group of 10• Average weight - 18-22gm• Orally, i.p. or s.c. dosage of test or
standard compound (e.g. Diazepam 3 mg/kg) or the vehicle.
• After 30 min i.p. or s.c injection or 60 min after oral dosing 60 mg/kg hexobarbital is injected i.v route
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• The animals are placed on their backs on a warmed (37 C) pad and the duration of loss of righting reflex( starting time of hexobarbital injection) is measured.
• Injection of hexobarbital usually cause anesthesia for about 15 min.
Procedure cont ….
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Evaluation:-
• Mean value of duration of anesthesia are recorded in control and experimental group
• % change in duration of anesthesia is calculated
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2.Experimental insomnia in rats• Developed by james and piper 1978• The compounds are tested in normal
animals where they do not significantly decrease weakfulness.
Procedure:-• Male wistar rate 200-275gm prepared
for chronic electroencephalographic and electomyographic recording.
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2.Experimental insomnia in rats Cont.
• Four silver/silver chloride electrode and two disc nuchal electrode are implanted
• Minimum10days allowed for recovery from surgery
• Animals are placed into sound-attenuated recording chamber with grid floor.
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Procedure cont….
• On the control day, the animals are dosed with the vehicle and control nonstress recording is obtained for 8hrs.
• Next day the animals are again injected and then exposed to electric footshock for 8hrs
• The footshock is delivered through grid floor of the recording chamber
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Cont….• During the footshock the EEG and
EMG recording circuits are automatically interrupted
• On the next day the rats are dosed with the test compound or the standard and recording are obtained during a shock session of 8hrs
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Evaluation• The sleep wake cycle is definitely
altered by the stress procedure .• The amount of arousal and of slow
wave sleep 1 are increased .• Slow wave 2nd and paradoxical sleep
decreased.• Phenobarbitone and benzodiazepines
antagonize these change at least partially.
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3. EEG REGISTRATION IN CONSCIOUS CATS
Principle The effect of hypnotics on sleep
pattern of EEG tracings can be studied in conscious, freely moving cats with chronically implanted electrode
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Procedure
• Female cats weighing 2.5-3.5 kg are anesthetized and prepared with bipolar subcortical electrodes in the reticular formation,dorsal hippocampus,and either amygdala,caudate necleus
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Procedure cont….
• Cortical screw electrode are placed over the anterior suprasylvian,lateral,medial suprasylvian ectosylvian gyri
• Two teflon coated steel wires are placed in the cervical neck muscles
All wires are connected to a subminiature
socket and implanted in dental acrylic
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Cont….
• Cats of this chronic colony are then intermittently utilized for drug experiments at interdrug intervals of at least two weeks
• Cats are taken into an experimental chamber 70, 80 cm high
• The box is lighted and ventilated with room air at 21 c
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Cont….
• The cat is immediately connected to a cable which exits through the top center of the cage into a mercury swivel
• Recording of the cortical EEG, cervical neck muscle tone and reticular formation multiple unit activity
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Evaluation
• The data are analyzed by analysis of variance with subjects, days , and drug as factors
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References
• Vogel. H. G, “Drug Discovery and Evaluation” second edition, page no.495-499