Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects.
The effects of haloperidol, alone and in combination with atropine, were compared with the effects of clozapine, alone and in combination with physostigmine, in a variety of tests commonly used to characterize neuroleptic compounds. It was found that clozapine in combination with physostigmine did not present the profile of activity of a classical neuroleptic agent; neither did haloperidol in combination with atropine present that of clozapine. In fact, some effects of haloperidol (catalepsy) were antagonized by atropine, while others (induction of striatal DA-receptor hypersensitivity) were enhanced. It is concluded that the interaction between dopaminergic and cholinergic systems in the striatum is highly complex, and that a neuroleptic possessing both potent DA-receptor blocking and muscarinic anticholinergic activity, while being less likely to cause parkinsonism in patients, would be more likely to induce tardive dyskinesias.
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D001285:Atropine; D010830:Physostigmine; D003024:Clozapine; D006220:Haloperidol; D006719:Homovanillic Acid