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Pharmacology, biochemistry, and behavior

Fourth ventricle effects of nicotine, 2-methylpiperidine and cytisine in dogs.


PMID 3786343

Abstract

Four distinguishable nicotinic binding sites have been identified as well as four nicotinic ligands with different specificities: (+/-)-2-methylpiperidine which binds to a very high affinity site (Site 1) and produces up-regulation of the high affinity site (Site 2); (-)-nicotine which binds to Site 1 and Site 2 as well as to a low affinity site (Site 4); (+)-nicotine which binds to Site 1, Site 4 and Site 3 which is also a high affinity site; and (-)-cytisine which binds to Sites 1 and 2. These drugs were injected into the 4th ventricle of 5 dogs in graded concentrations (12.5 to 400 micrograms) and their effects on the EEG, skin twitch reflex latency, heart rate, rectal temperature, pupillary diameter, blood pressure and the amplitude of the flexor reflex were measured. Drugs which act predominantly on Site 1 [(+/-)-2-methylpiperidine and (+)-nicotine] produced EEG synchronization and hyperalgesia while drugs which interact with Sites 2 and 4 produce EEG desynchronization, analgesia and tachycardia. These data indicate that nicotinic ligands which have different binding specificities have different actions in medullary function and support the hypothesis that the different binding sites have different pharmacologic significance.

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