The hypotensive effect of BMY 7378 involves central 5-HT1A receptor stimulation in the adult but not in the young rat.

Abstract

BACKGROUND:

Stimulation of central 5-hydroxytryptamine-1A (5-HT(1A)) receptors produces hypotension and bradycardia. We describe BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9 dione) effects in cardiovascular function and [(3)H] 8-OH-DPAT (8-hydroxy-2-(di-n-propyl-amino) tetralin) binding sites in rat brain of different ages.

METHODS:

BMY 7378 was administered to anesthetized male Wistar rats (1, 3 and 6 months old) and blood pressure and heart rate were continuously recorded. Saturation of [(3)H] 8-OH-DPAT binding to 5-HT(1A) sites in brain membranes was determined.

RESULTS:

Basal diastolic blood pressure increased with age, 85 +/- 2, 106 +/- 3, and 113 +/- 2 mmHg for 1-, 3- and 6-month-old rats, respectively (p <0.05 among groups). BMY 7378 induced significant dose- and age-dependent hypotension. The selective 5-HT(1A) receptor antagonist, WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]N-(2-pyridinyl) cyclohexanecarboxamide), antagonized BMY 7378 effects in 6 month-old but not in younger rats. [(3)H] 8-OH-DPAT binding sites decreased in hippocampi and brainstem with maturation.

CONCLUSIONS:

Data suggest that BMY 7378 is a hypotensive agent in the rat, but that its actions are mediated, in part, by central 5-HT(1A) receptor stimulation in the adult and by a nonserotonergic mechanism in the young rat.

• Authors: Rafael Villalobos-Molina, Miguel Gil-Flores, Itzell A Gallardo-Ortiz, J Javier López-Guerrero, Maximiliano Ibarra
• Journal: Archives of medical research (Arch Med Res) 2004 Nov-Dec Vol. 35 Issue 6 Pg. 495-8 ISSN: 0188-4409 [Print] United States
• PMID: 15631873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Piperazines
• Receptor, Serotonin, 5-HT1A
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• BMY 7378

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (chemistry, metabolism)
• Adrenergic alpha-Antagonists (pharmacology)
• Aging (physiology)
• Animals
• Blood Pressure (drug effects)
• Heart Rate
• Hypotension
• Male
• Piperazines (pharmacology)
• Radioligand Assay
• Rats
• Rats, Wistar
• Receptor, Serotonin, 5-HT1A (metabolism)