Anti-dopaminergic and anti-muscarinic effects of dibenzodiazepines: relationship to drug induced Parkinsonism.
1. The anti-dopaminergic effects of several dibenzodiazepines were examined on the dopamine-stimulated adenylate cyclase in rat striatal homogenates. The "cis" isomer of clozapine, HF-2046, was the most potent in this respect and perlapine, which is devoid of neuroleptic activity, was the weakest. 2. The anti-muscarinic effects of the same compounds were measured by using the muscarinic affinity label 3H-propylbenzilylcholine mustard. HF-2046 was the most potent and loxapine the least potent of the drugs used. 3. The anti-dopaminergic effects of the drugs correlate well with neuroleptic but not with extrapyramidal effects. The anti-dopaminergic/anti-muscarinic ratio, however, correlates well with extrapyramidal rather than neuroleptic effects.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology; D003984:Dibenzazepines / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000494:pharmacology; D018492:Dopamine Antagonists; D006719:Homovanillic Acid / Q000378:metabolism; D008152:Loxapine / Q000494:pharmacology; D008297:Male; D010276:Parasympatholytics; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects
D003984:Dibenzazepines; D003987:Dibenzothiazepines; D018492:Dopamine Antagonists; D010276:Parasympatholytics; D010879:Piperazines; D011950:Receptors, Cholinergic; C003910:perlapine; D000262:Adenylyl Cyclases; D003024:Clozapine; D008152:Loxapine; D002794:Choline; D006719:Homovanillic Acid