The Influence of Mecamylamine on Trigeminal and Olfactory Chemoreception of Nicotine

Nicotine presented to the nasal cavity at low concentrations evokes 'odorous' sensations, and at higher concentrations 'burning' and 'stinging' sensations. A study in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(-)-nicotine and the perceived pleasantness/unpleasantness following nasal stimulation with S-(-)-nicotine. Mecamylamine, a nicotinic acetylcholine-receptor-(nAch-R) antagonist, was able to block painful responses following chemical stimulation of the human tongue and to block responses from the rat's ethmoidal nerve. The aim of our study in humans was to investigate the effects of mecamylamine on the olfactory and the trigeminal chemoreception of nicotine enantiomers. In order to achieve this aim, we determined-before and after mecamylamine-(1) detection thresholds, trigeminal thresholds, and intensity estimates (stimulus intensity) and (2) recorded the negative mucosal potential (NMP) following nasal stimulation with nicotine in a placebo-controlled double blind study (n = 15). CO(2) was used as a trigeminal and H(2)S as an olfactory control stimulus. Mecamylamine significantly increased trigeminal thresholds of S-(-)-nicotine and reduced intensity estimates and NMPs following stimulation with nicotine enantiomers, whereas mecamylamine did not influence NMPs and trigeminal intensity estimates following stimulation with CO(2). In contrast, mecamylamine did neither influence detection thresholds nor olfactory intensity estimates following stimulation with olfactory nicotine concentrations. These results demonstrate that the trigeminal nasal chemoreception of nicotine enantiomers, in contrast to CO(2), is mediated by nAch-Receptors and give evidence that the olfactory chemoreception of nicotine is independent from peripheral nAch-Receptors.