Abstract |
The effect of NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido]-butyl] piperazine), described as a mixed 5-HT(1A) receptor agonist/antagonist, on cardiovascular function was studied. The i.v. injection of NAN-190 (1-300 micro/kg) dose-dependently decreased blood pressure (p<0.001), while heart rate was not significantly modified compared to saline-treated, anaesthetized adult rats. WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide), a highly selective 5-HT(1A) receptor antagonist, increased NAN-190-induced hypotension (p<0.05). In the pithed rat NAN-190 displaced the phenylephrine dose-pressor response curve to the right; ED(50) values were: approximately 14, 20, 40 and 270 microg/kg for saline and NAN-190 (1, 10 and 100 microg/kg, respectively); similar ED(50) values were obtained with prazosin ( approximately 20, 69 and 358 microg/kg for 1, 10 and 100 microg/kg of prazosin, respectively). NAN-190 shifted to the right the concentration-response curves to phenylephrine in rat tail artery (alpha(1A)-adrenoceptors), in rabbit aorta (alpha(1B)-adrenoceptors) and in rat aorta (alpha(1D)-adrenoceptors), with pA(2) values of 9.47, 9.02 and 9.99; while Schild slopes were -0.78, -1.13 and -0.90, respectively (not significantly different from unity). The results show that NAN-190 induced hypotension in the anaesthetized, adult rat and suggest that this effect could be explained by antagonism of vascular alpha(1)-adrenoceptors.
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Authors | Rafael Villalobos-Molina, Itzell A Gallardo-Ortíz, J Javier López-Guerrero, Maximiliano Ibarra |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 455
Issue 1
Pg. 59-64
(Nov 22 2002)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 12433595
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic alpha-1 Receptor Antagonists
- Piperazines
- Serotonin Antagonists
- 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
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Topics |
- Adrenergic alpha-1 Receptor Antagonists
- Animals
- Hypotension
(chemically induced)
- Male
- Muscle, Smooth, Vascular
(drug effects)
- Piperazines
(adverse effects, pharmacology)
- Rabbits
- Rats
- Rats, Wistar
- Serotonin Antagonists
(adverse effects, pharmacology)
- Vasoconstriction
(drug effects)
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