The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 receptors.
BACKGROUND
Nonselective muscarinic acetylcholine antagonists have been used for several years as antiparkinsonian drugs. However, there are at least five subtypes of muscarinic receptor (M1-5). Neostriatal M4 receptors have been implicated in aspects of motor function, and it has been suggested that M4 antagonists could be used as treatments for parkinsonism.


OBJECTIVE
Currently, there is a lack of highly selective M4 antagonists that readily penetrate the blood brain barrier. Thus, the present studies focused upon the effects of tropicamide, a muscarinic acetylcholine receptor antagonist with moderate binding selectivity for the M4 receptor subtype.


METHODS
Tremulous jaw movements were used as a model of parkinsonian tremor in these studies, and the effects of tropicamide were compared with those of the nonselective muscarinic antagonist atropine.


RESULTS
Tropicamide suppressed the tremulous jaw movements induced by the muscarinic agonist pilocarpine and the dopamine antagonist pimozide. Analysis of the dose-response curves indicated that tropicamide showed approximately the same potency as atropine for suppression of pilocarpine-induced jaw movements but was more potent than atropine on the suppression of pimozide-induced jaw movements. In contrast, atropine was more potent than tropicamide in terms of impairing performance on visual stimulus detection and delayed nonmatch-to-position tasks.


CONCLUSIONS
These studies demonstrate that tropicamide, which currently is used clinically for ophthalmic purposes, can exert actions that are consistent with antiparkinsonian effects. Moreover, the different pattern of effects shown by tropicamide compared to those of atropine on motor vs cognitive tasks could be due to the modest M4 selectivity shown by tropicamide.
Betz
Adrienne J
AJ
Behavioral Neuroscience, Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
McLaughlin
Peter J
PJ
Burgos
Melissa
M
Weber
Suzanne M
SM
Salamone
John D
JD
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007568:Jaw / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010862:Pilocarpine; D010868:Pimozide; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043588:Receptor, Muscarinic M4 / Q000187:drug effects* / Q000378:metabolism; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D014331:Tropicamide / Q000008:administration & dosage / Q000494:pharmacology*; D014796:Visual Perception / Q000187:drug effects
D018492:Dopamine Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043588:Receptor, Muscarinic M4; D010862:Pilocarpine; D010868:Pimozide; D001285:Atropine; D014331:Tropicamide