Indorenate is a 5‐HT1A receptor agonist with antihypertensive properties. This study was aimed to determine if indorenate, like other 5‐HT1A 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‐HT1A receptors and, to a lesser extent, for α1‐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‐HT1/5‐HT2 receptor antagonist), but not pindolol (a β‐adrenoceptor and 5‐HT1 receptor blocker), antagonized the pressor responses produced by both agonists; only the pressor effects of 8‐OH‐DPAT, however, were antagonized by prazosin (an α1‐adrenoceptor antagonist). Interestingly, ketanserin (a 5‐HT2 and α1‐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 α1‐adrenoceptors whereas indorenate produced pressor effects probably due to stimulation of 5‐HT2 receptors. Thus, 8‐OH‐DPAT, but not indorenate, showed activity at α1‐adrenoceptors in the pithed rat.
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Castillo et al. (1994) studied this question.
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