Indorenate is a 5-HT1A receptor agonist with antihypertensive properti
es. This study was aimed to determine if indorenate, like other 5-HT1A
receptor agonists, may also interact with a-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 alpha(1)-adrenoceptors) on the blood pressure of pithed ra
ts were compared. Both compounds produced dose-dependent increases in
blood pressure; 8-OH-DPAT was the most potent whereas indorenate produ
ced a higher maximum effect. Metitepine (a mixed 5-HT1/5-HT2 receptor
antagonist), but not pindolol (a beta-adrenoceptor and 5-HT1 receptor
blocker), antagonized the presser responses produced by both agonists;
only the presser effects of 8-OH-DPAT, however, were antagonized by p
razosin (an alpha(1)-adrenoceptor antagonist). Interestingly, ketanser
in (a 5-HT2 and alpha(1)-adrenoceptor blocker) strongly antagonized th
e presser responses to indorenate whereas only a slight inhibition of
8-OH-DPAT responses was observed. Further, in pithed rats intravenousl
y infused with norepinephrine (NE), 8-OH-DPAT, but not indorenate, pro
duced dose-dependent hypotensive effects and both compounds were inact
ive in rats infused with quipazine. In conclusion, 8-OH-DPAT behaved a
s a partial agonist at alpha(1)-adrenoceptors whereas indorenate produ
ced presser effects probably due to stimulation of 5-HT2 receptors. Th
us, 8-OH-DPAT, but not indorenate, showed activity at alpha(1)-adrenoc
eptors in the pithed rat. (C) 1994 Wiley-Liss, Inc.