TREMULOUS JAW MOVEMENTS INDUCED BY THE ACETYLCHOLINESTERASE INHIBITORTACRINE - EFFECTS OF ANTIPARKINSONIAN DRUGS

Several experiments were conducted to study the effects of established or potential antiparkinsonian drugs on the tremulous jaw movements in duced by the anticholinesterase tacrine (9-amino-1,2,3,4-tetrahydroami noacridine hydrochloride). In the first group of four experiments, sep arate groups of animals that received 2.5 or 5.0 mg/kg tacrine showed a dose-dependent decrease in tremulous jaw movements following co-admi nistration of the non-selective dopamine receptor agonist apomorphine, the full dopamine D-2 receptor agonist bromocriptine, and the full do pamine D-1 receptor agonist APE lyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-b enzazepine). Co-administration of the partial dopamine D-1 receptor ag onist SKF 38393 (R(+)-2,3,4,5-tetrahydro-7,8-dihy droxy-1-phenyl-1H-be nzazepine; 7.5-30.0 mg/kg) did not reduce tremulous jaw movements prod uced by 2.5 or 5.0 mg/kg tacrine. In animals treated with 2.5 mg/kg ta crine, co-administration of SKF 38393 resulted in a dose-related trend towards a potentiation of tremulous jaw movements. In the second grou p of experiments, all rats received 2.5 mg/kg tacrine. The dopamine pr ecursor L-DOPA (L-3,4-dihydroxyphenylalanine), the dopamine and norepi nephrine releasing agent amantadine, and the muscarinic receptor antag onist benztropine all reduced tremulous jaw movements induced by 2.5 m g/kg tacrine. Across all experiments, it was noted that apomorphine, b romocriptine and benztropine were more potent than amantadine and L-DO PA. These results are broadly consistent with the therapeutic doses of these agents noted in the clinical literature. The results of these e xperiments indicate that tremulous jaw movements in rats may be a usef ul model for evaluating potential antiparkinsonian agents. (C) 1997 El sevier Science B.V.