Re-evaluation of the selectivity of 2-N,N-dimethylamino-5,6-dihydroxy-1,2,3, 4-tetrahydronaphthalene (M-7) as an agonist of postjunctional alpha-2 adrenoceptors in the pithed normotensive rat.

The quality of the postjunctional alpha adrenoceptors involved in the increase in diastolic pressure caused by 2-N,N-dimethylamino-5, 6-dihydroxy-1,2,3,4-tetrahydronaphthalene (M-7) were re-evaluated in pithed normotensive rats. The antagonism by yohimbine (1 mg/kg) was most pronounced, whereas prazosin (0.1 mg/kg) had no effect on the hypertensive responses to low doses of M-7, but clearly attenuated those to the higher amounts (greater than 10 micrograms/kg i.v.). A pretreatment with the combination of both alpha adrenoceptor antagonists markedly depressed slope and maximum of the log dose-pressor response curve to M-7. The selective beta-2 adrenoceptor antagonist ICI 118, 551 caused an enhancement of the pressor effects of the higher doses of M-7 which was most profound after the combined treatment with prazosin and yohimbine. M-7 showed a dose-dependent depressor effect in phentolamine (30 mg/kg)-treated pithed rats of which diastolic pressure was raised by infusion of vasopressin. It is concluded that M-7, in addition to its reported alpha-2 adrenoceptor agonistic properties, stimulates postsynaptic alpha-1 adrenoceptors in higher doses. In pithed normotensive rats, however, M-7 also interacts with vascular beta-2 adrenoceptors giving rise to vasodilatation. This action can strongly interfere with the vasoconstrictor effect of M-7.