Tremulous jaw movements induced by the acetylcholinesterase inhibitor tacrine: effects of antiparkinsonian drugs.

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Cousins MS, Carriero DL, Salamone JD

Tremulous jaw movements induced by the acetylcholinesterase inhibitor tacrine: effects of antiparkinsonian drugs.

Eur J Pharmacol. 1997 Mar 19;322(2-3):137-45.

PubMed ID

9098680 [ View in PubMed

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Abstract

Several experiments were conducted to study the effects of established or potential antiparkinsonian drugs on the tremulous jaw movements induced by the anticholinesterase tacrine (9-amino-1,2,3,4-tetrahydroaminoacridine hydrochloride). In the first group of four experiments, separate groups of animals that received 2.5 or 5.0 mg/kg tacrine showed a dose-dependent decrease in tremulous jaw movements following co-administration of the non-selective dopamine receptor agonist apomorphine, the full dopamine D2 receptor agonist bromocriptine, and the full dopamine D1 receptor agonist APB (R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine). Co-administration of the partial dopamine D1 receptor agonist SKF 38393 (R(+)-2,3,4,5-tetrahydro-7,8-dihydroxy-l phenyl-1 H-benzazepine: 7.5-30.0 mg/kg) did not reduce tremulous jaw movements produced by 2.5 or 5.0 mg/kg tacrine. In animals treated with 2.5 mg/kg tacrine, co-administration of SKF 38393 resulted in a dose-related trend towards a potentiation of tremulous jaw movements. In the second group of experiments, all rats received 2.5 mg/kg tacrine. The dopamine precursor L-DOPA (L-3,4-dihydroxyphenylalanine), the dopamine and norepinephrine releasing agent amantadine, and the muscarinic receptor antagonist benztropine all reduced tremulous jaw movements induced by 2.5 mg/kg tacrine. Across all experiments, it was noted that apomorphine, bromocriptine and benztropine were more potent than amantadine and L-DOPA. These results are broadly consistent with the therapeutic doses of these agents noted in the clinical literature. The results of these experiments indicate that tremulous jaw movements in rats may be a useful model for evaluating potential antiparkinsonian agents.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amantadine	Dopamine D2 receptor	Protein	Humans	Yes	Agonist	Details