title: The hypotensive effect of BMY 7378 is antagonized by a silent 5-HT(1A) receptor antagonist: comparison with 8-hydroxy-dipropylamino tetralin.
abstract: BACKGROUND
  Stimulation of central 5-HT(1A) receptors produces bradycardia and diminishes blood pressure in conscious or anesthetized rats. Our objective was to investigate the effects on blood pressure and heart rate of the partial 5-HT(1A) receptor agonist and selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro [4.5] decane-7,9 dione hydrochloride) compared to the full 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-dipropylamino tetralin) in adult anesthetized rats.
  
  
  METHODS
  Male Wistar rats of 6 months of age were exposed intravenously (i.v.) to increasing doses of BMY 7378 or 8-OH-DPAT in the absence and presence of WAY 100635. Blood pressure and heart rate were continuously recorded.
  
  
  RESULTS
  BMY 7378 induced a decrease in blood pressure with no apparent change in heart rate compared to basal values, while 8-OH-DPAT decreased both hemodynamic parameters. BMY 7378 hypotensive effect was antagonized by the selective, silent 5-HT(1A) receptor antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). However, a remnant yet significant hypotensive effect was not blocked by the antagonist. In contrast, 8-OH-DPAT actions were completely blocked by WAY 100635.
  
  
  CONCLUSIONS
  Data suggest that BMY 7378 cardiovascular effects are related to activation, as a full agonist, of central 5-HT(1A) receptors in adult rats; however, participation of other systems such as vascular alpha1-adrenoceptors in cardiovascular function is suggested.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Instituto Politécnico Nacional (IPN), Mexico City, Mexico. raffaeld@prodigy.net.mx
authors.forename: R
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: J J
authors.initials: JJ
authors.lastname: López-Guerrero
authors.forename: M
authors.initials: M
authors.lastname: Ibarra
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C053428:BMY 7378