Sodium phenobarbitone reverses the anxiogenic effects of compounds acting at three different central sites.
Sodium phenobarbitone was tested for its ability to antagonise the anxiogenic effects of compounds acting at three different central sites. These compounds were: FG 7142, a beta-carboline which acts at the benzodiazepine binding site on the GABA-benzodiazepine receptor complex; pentylenetetrazole, which acts at the picrotoxinin site on the GABA-benzodiazepine receptor complex; and yohimbine which is an antagonist at the alpha 2-adrenoceptor. The experiments were carried out in two tests of anxiety using rats. In the social interaction test (the test arena was familiar and dimly lit), FG 7142 (5 mg/kg) and pentylenetetrazole (15 mg/kg) reduced the time spent in social interaction (indicating anxiogenic activity); these effects were reversed by sodium phenobarbitone (35 mg/kg). Sodium phenobarbitone (35 mg/kg) alone decreased locomotor activity as measured in the social interaction test, which was reversed by pentylenetetrazole (15 mg/kg). In the elevated plus-maze, FG 7142 (6.7 mg/kg) pentylenetetrazole (20 mg/kg) and yohimbine (4 mg/kg) reduced the percentage of open-arm entries and the percentage of time spent on the open arms (indicating anxiogenic activity); these effects were reversed by sodium phenobarbitone (35 mg/kg). Sodium phenobarbitone (35 mg/kg) alone significantly increased the percentage of open-arm entries and the percentage of time spent on the open arms (indicating anxiolytic activity). This study, together with previous studies using other clinically-effective anxiolytic drugs, suggests that the ability of a compound to antagonise the effects of anxiogenic agents may be a useful indirect means of predicting anxiolytic activity.
Johnston
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Department of Pharmacology, School of Pharmacy, University of London, U.K.
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D000818:Animals; D001007:Anxiety; D001067:Appetite Depressants / Q000037:antagonists & inhibitors*; D002243:Carbolines / Q000037:antagonists & inhibitors*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D012919:Social Behavior; D015016:Yohimbine / Q000037:antagonists & inhibitors*
D001067:Appetite Depressants; D002243:Carbolines; D011942:Receptors, Adrenergic, alpha; D011963:Receptors, GABA-A; D015016:Yohimbine; C035874:FG 7142; D010433:Pentylenetetrazole; D010634:Phenobarbital