Effects of WAY 100635 and (-)-5-Me-8-OH-DPAT, a novel 5-HT1A receptor antagonist, on 8-OH-DPAT responses.

Abstract

The neurochemical profile at both post and presynaptic 5-HT1A receptors of a novel 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) analog, 5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin ¿(+/-)-5-Me-8-OH-DPAT¿ and its stereoisomers was determined and compared to that of the highly selective 5-HT1A receptor antagonist, N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide (WAY 100635). We evaluated their effects on 8-OH-DPAT-induced decrease in cAMP production, on 8-OH-DPAT-induced decrease in rat ventral hippocampal extracellular 5-hydroxytryptamine (5-HText) levels and in body temperature in mice. Both (+/-)- and (-)-5-Me-8-OH-DPAT blocked the 8-OH-DPAT-induced inhibition of forskolin-stimulated cAMP production. Moreover, while having no significant effect when injected alone, (+/-)-, (-)-5-Me-8-OH-DPAT and WAY 100635 antagonized the 8-OH-DPAT-induced decrease in 5-HText in rats and hypothermia in mice. By contrast, the (+) isomer inhibited the cAMP synthesis and did not modify the 8-OH-DPAT response on 5-HText in ventral hippocampus. These data suggest that (+/-)-5-Me-8-OH-DPAT acts selectively, its activity residing in the (-) enantiomer, this latter compound acting similarly to WAY 100635 as a full, selective and silent 5-HT1A antagonist.

• Authors: A C Trillat, I Malagié, M Mathé-Allainmat, M C Anmela, C Jacquot, M Langlois, A M Gardier
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 347 Issue 1 Pg. 41-9 (Apr 17 1998) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9650846 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 5-methyl-8-hydroxy-2-(di-n-propylamino)tetralin
• Piperazines
• Pyridines
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Colforsin
• Serotonin
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Cyclic AMP
• Adenylyl Cyclases

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (analogs & derivatives, pharmacology)
• Adenylyl Cyclases (metabolism)
• Animals
• Body Temperature (drug effects)
• Colforsin (antagonists & inhibitors, pharmacology)
• Cyclic AMP (biosynthesis)
• Drug Interactions
• Female
• Hippocampus (drug effects, enzymology, metabolism)
• Male
• Mice
• Microdialysis
• Piperazines (pharmacology)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (drug effects)
• Receptors, Serotonin, 5-HT1
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Stereoisomerism
• Stimulation, Chemical