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Direct effects of indorenate and 8‐OH‐DPAT on the blood pressure of pithed rats
Author(s) -
Castillo Carlos,
Ibarra Maximiliano,
Terron Jósé A.,
Villalón Carlos M.,
Hong Enrique
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430330104
Subject(s) - pindolol , prazosin , ketanserin , endocrinology , chemistry , medicine , agonist , 8 oh dpat , quipazine , receptor , antagonist , 5 ht receptor , pharmacology , serotonin
Indorenate is a 5‐HT 1A receptor agonist with antihypertensive properties. This study was aimed to determine if indorenate, like other 5‐HT 1A receptor agonists, may also interact with α‐adrenoceptors. Therefore, the effects of indorenate and 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT; which has affinity for 5‐HT 1A receptors and, to a lesser extent, for α 1 ‐adrenoceptors) on the blood pressure of pithed rats were compared. Both compounds produced dose‐dependent increases in blood pressure; 8‐OH‐DPAT was the most potent whereas indorenate produced a higher maximum effect. Metitepine (a mixed 5‐HT 1 /5‐HT 2 receptor antagonist), but not pindolol (a β‐adrenoceptor and 5‐HT 1 receptor blocker), antagonized the pressor responses produced by both agonists; only the pressor effects of 8‐OH‐DPAT, however, were antagonized by prazosin (an α 1 ‐adrenoceptor antagonist). Interestingly, ketanserin (a 5‐HT 2 and α 1 ‐adrenoceptor blocker) strongly antagonized the pressor responses to indorenate whereas only a slight inhibition of 8‐OH‐DPAT responses was observed. Further, in pithed rats intravenously infused with norepinephrine (NE), 8‐OH‐DPAT, but not indorenate, produced dose‐dependent hypotensive effects and both compounds were inactive in rats infused with quipazine. In conclusion, 8‐OH‐DPAT behaved as a partial agonist at α 1 ‐adrenoceptors whereas indorenate produced pressor effects probably due to stimulation of 5‐HT 2 receptors. Thus, 8‐OH‐DPAT, but not indorenate, showed activity at α 1 ‐adrenoceptors in the pithed rat. © 1994 Wiley‐Liss, Inc.