Effects of some antimuscarinics alone and in combination with chlordiazepoxide on punished and nonpunished behavior of rats.
Since both diphenyl-substituted antimuscarinics and benzodiazepine anxiolytic drugs have been reported to increase responding under fixed-ratio schedules of food presentation, these antimuscarinics may also have anxiolytic activity. The effects of aprophen and benactyzine on punished responding of rats, a preclinical anxiolytic drug screen, were compared with those of atropine and chlordiazepoxide. None of the antimuscarinics produced consistent overall increases in behavior suppressed by punishment, in contrast to the dose-dependent increases obtained with chlordiazepoxide. Aprophen did not potentiate the anxiolytic activity of chlordiazepoxide. However, a high dose of atropine potentiated the effects of chlordiazepoxide on punished responding. Thus the diphenyl-substituted antimuscarinics, aprophen and benactyzine, do not possess consistent or robust anxiolytic activity in this preclinical screen. The previously reported behavioral excitatory effects of these compounds may therefore be unrelated to this pharmacological action.
Witkin
J M
JM
Drug Development Group, NIDA Addiction Research Center, Baltimore, MD 21224.
Witkin
K M
KM
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001535:Benactyzine / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D011678:Punishment; D051381:Rats; D011919:Rats, Inbred Strains
D010276:Parasympatholytics; D001535:Benactyzine; D002707:Chlordiazepoxide; D001285:Atropine