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8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increases plasma glucose levels in conscious rats probably by stimulation of central 5-HT1A receptors. We have examined the effects of WAY100135 (N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpropan amide), a selective 5-HT1A receptor antagonist and its enantiomers on plasma glucose levels and on the hyperglycaemia induced by 8-OH-DPAT. (R,S)-WAY100135 (minimum effective dose (MED) 3 mg/kg i.v.) and (S)-WAY100135 (MED 1 mg/kg i.v.) dose-dependently attenuated 8-OH-DPAT-induced hyperglycaemia. In contrast, (R)-WAY100135 at doses up to 3 mg/kg i.v. was unable to block hyperglycaemia induced by 8-OH-DPAT. When the antagonists were examined for intrinsic effects on plasma glucose levels only (S)-WAY100135 (3 mg/kg i.v.) caused a significant but transient hyperglycaemia (20% increase). These results are consistent with previous suggestions that (R,S)-WAY100135 and (S)-WAY100135 are selective 5-HT1A receptor antagonists and that 8-OH-DPAT-induced hyperglycaemia is mediated by 5-HT1A receptors. The antagonist action of WAY100135 is stereoselective, and more potent activity being observed with the (S) enantiomer.

Type

Journal article

Journal

Eur J Pharmacol

Publication Date

11/03/1994

Volume

254

Pages

133 - 139

Keywords

8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Blood Glucose, Dose-Response Relationship, Drug, Hyperglycemia, Male, Piperazines, Prazosin, Rats, Rats, Sprague-Dawley, Receptors, Adrenergic, alpha-1, Serotonin Antagonists, Serotonin Receptor Agonists, Stereoisomerism