Anti-nicotinic properties of anticholinergic antiparkinson drugs

The nature of the antagonism by anticholinergic compounds of nicotine-induc ed convulsion in mice has not been defined clearly. Although, because they do not compete effectively for agonist binding to brain tissue in-vitro, th ese compounds are thought to be non-competitive antagonists in the brain, p harmacological evidence is lacking. This study describes the anti-nicotinic properties of the clinically used anticholinergic antiparkinson drugs, ben ztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphe nidyl. Nicotine-induced convulsion and arecoline-induced tremor in mice were effec tively prevented by these drugs. The concentrations of benztropine, biperid en, caramiphen, ethopropazine, procyclidine and trihexyphenidyl affording 5 0% prevention of nicotine-induced convulsion (ED50 values) were 7.4, 4.6, 7 .8, 4.9, 3.1 and 3.3 mgkg(-1) respectively. The classical muscarinic recept or antagonist atropine had potent anti-muscarinic effects but very weak ant i-nicotinic activity. The classical nicotinic receptor antagonist mecamylam ine had potent anti-nicotinic activity but no anti-muscarinic effects. The pattern of shift of the dose-response curve for nicotine-induced convulsion in mice was determined in the presence of increasing concentrations of the anticholinerpic antiparkinson drugs. These drugs were found to increase th e ED50 (0.49 mgkg(-1)) of nicotine-induced convulsion in a dose-related man ner. The maximum effect of nicotine and the slope of nicotine dose-response curve were not significantly influenced by either low or high doses of ben ztropine, procyclidine or trihexylphenidyl, which suggests competitive acti on. Biperiden, caramiphen and ethopropazine, at low doses which significant ly increased the ED50 of nicotine, did not affect the maximum effect of nic otine or the slope of the nicotine dose-response curve; at higher doses, ho wever, they reduced the maximum effect and the slope, which suggests that t hese drugs have both competitive and non-competitive properties in antagoni zing nicotine-induced convulsion in mice. The experiments demonstrate that the anticholinergic antiparkinson drugs an d mecamylamine effectively antagonize nicotine-induced convulsion, but atro pine does not; some of these drugs have competitive properties whereas othe rs seem to have both competitive and non-competitive properties in antagoni zing nicotine-induced convulsion in mice.