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Mécanisme d'Action de la Cotinine : Interactions Nicotiniques, Étude Pharmacocinétique et Pharmacodynamique, Identification et Purification de son Récepteur

Abstract : The comparative studies of nicotine and its derivative, resulted by ketone grafting at the α position to the nitrogen of the pyrrolidine ring, were investigated by distinct experimental means : toxic interactions in flies and mice, binding to the peripheral and to neuronal nicotinic acetylcholine receptors, blood-brain barrier permeability and its modulation, use of [125I]cotinine to study cotinine receptors, autoradiographic distribution of cotinine receptors, nicotine or cotinine induced modulation of neuronal nicotinic acetylcholine receptors and affinity chromatography purification of cotinine receptors.
The results of the experiments, performed under our conditions, reveal that nicotine metabolism :
1 - lowers its toxicity by 50, by spraying, in flies and 250 times, by intraperitoneal route, in mice.
2 - produces an oxide derivative (cotinine), relatively low active and a demethyl derivative (nornicotine), relatively very active.
The former acts with nicotine by distinct mechanisms (supra-additive or synergism), while the later acts with nicotine by common mechanisms (additive or antagonism).
Hexamethonium did not protect against nicotine and cotinine mixtures toxicity suggesting a central effect.
3 - lowers its affinity for peripheral and major neuronal nicotinic acetylcholine receptors.
4 - lowers its ability to pass the blood-brain barrier, in the vigilant rat, and subjects this passage to the control of peripheral nicotinic mechanisms.
5 - lowers and modifies its modulator actions on neuronal nicotinic acetylcholine receptors.
6 - enhances its selectivity for minor subtypes of neuronal nicotinic acetylcholine receptors.

Thus, nicotine metabolism lowers its toxicity and its activities, and directs beneficially its pharmacological properties by enhancing its selectivity for subtypes of neuronal nicotinic acetylcholine receptors
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Contributor : Victor Omar Riah <>
Submitted on : Friday, October 16, 2009 - 12:53:35 PM
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Victor Riah. Mécanisme d'Action de la Cotinine : Interactions Nicotiniques, Étude Pharmacocinétique et Pharmacodynamique, Identification et Purification de son Récepteur. Biochimie [q-bio.BM]. Institut National Polytechnique de Toulouse - INPT, 1996. Français. ⟨tel-00424554⟩

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