On the effects and mechanism of action of the antihypertensive agent TR 3369 (5-methoxytryptamine beta-methylcarboxylate) in spontaneously hypertensive rats.

The effects of the serotonin (5-HT) analog TR 3369 (5-methoxytryptamine beta-methylcarboxylate) on blood pressure and heart rate of spontaneously hypertensive rats (SHR) were examined. In conscious SHR, TR 3369 caused reductions in blood pressure without importantly changing heart rate in doses ranging from 1 to 30 mg/kg p.o. TR 3369 was found to have no significant antagonistic effects on alpha-, beta-, or 5-HT receptors, nor did the drug inhibit adrenergic neuronal or ganglionic function. A slight but unimportant effect on angiotensin II pressor responses was noted. Therefore, the data are in agreement with the suggestion that TR 3369 acts through a central mechanism of action. The 5-HT antagonist cinanserin had little effect on blood pressure of SHR when administered alone, whereas it markedly reduced the duration, but not the magnitude, of the TR 3369 antihypertensive action in SHR. It is suggested that at least a portion of the antihypertensive effect of TR 3369 involves activation of central 5-HT receptors.