The hypotensive effect of BMY 7378 involves central 5-HT1A receptor stimulation in the adult but not in the young rat.
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.
Villalobos-Molina
Rafael
R
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados- IPN, Sede Sur, México City, México. rvillalobosm@att.net.mx
Gil-Flores
Miguel
M
Gallardo-Ortiz
Itzell A
IA
López-Guerrero
J Javier
JJ
Ibarra
Maximiliano
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000737:chemistry / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate; D007022:Hypotension; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C053428:BMY 7378