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.
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009284:Naphthols / Q000008:administration & dosage* / Q000494:pharmacology; D011224:Prazosin / Q000008:administration & dosage; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects; D015016:Yohimbine / Q000008:administration & dosage
D000317:Adrenergic alpha-Antagonists; D009284:Naphthols; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C009957:5,6-dihydroxy-2-dimethylaminotetralin; D011224:Prazosin