title: Pargyline reduces/prevents neuroleptic-induced acute dystonia in monkeys.
abstract: The neuropharmacologic mechanisms underlying neuroleptic-induced extrapyramidal syndromes (EPS) were studied using a nonhuman primate model. Twenty-six Cebus albifrons monkeys were given weekly challenges of haloperidol (0.025 mg/kg IM), and half of the animals received the monoamine oxidase (MAO) inhibitor pargyline (5 mg/kg PO) daily for 17 consecutive days during the protocol. Pargyline caused no changes in baseline behaviors, but significantly reduced haloperidol-induced acute dystonia (AD) (-67%, P less than 0.002) and parkinsonism (-56%, P less than 0.005). The majority (8 of 13) of the experimental group had complete prevention of neuroleptic-induced EPS during cotreatment with pargyline. Behavioral scores returned to baseline levels after stopping pargyline, and did not show the further sensitization to haloperidol-induced AD that occurred in the control group. The possible mechanisms by which an MAO inhibitor might influence neuroleptic-induced AD were considered. The most likely explanation would appear to involve facilitation of striatal dopamine (DA) neurotransmission by inhibition of intra- and extraneuronal MAO, thus supporting the hypothesis that AD is due to decreased striatal DA function with secondary cholinergic hyperfunction.
authors.affiliation: Department of Psychiatry, Oregon Health Sciences University, Portland.
authors.forename: R
authors.initials: R
authors.lastname: Heintz
authors.forename: D E
authors.initials: DE
authors.lastname: Casey
mesh_terms: D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000517:prevention & control; D002428:Cebus; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D004421:Dystonia / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D008995:Monoamine Oxidase / Q000502:physiology; D010293:Pargyline / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D010293:Pargyline; D008995:Monoamine Oxidase; D006220:Haloperidol; D004298:Dopamine