Pharmacological activity of ACC-7513, a selective alpha-adrenoceptor and 5-hydroxytryptamine receptor blocking agent.
The pharmacological activity of N-[2-(2,6-dimethoxyphenoxy) ethyl]-2-(2-methoxyphenoxy) ethanaminium chloride (ACC-7513) was determined in isolated smooth and cardiac muscle and its effect on blood pressure and heart rate assessed in the spontaneously hypertensive rat (SHR). ACC-7513 was found to be a potent alpha-adrenoceptor blocking agent (pA2:8.33) and a 5-hydroxytryptamine (5-HT) antagonist (pA2:7.01), both in rabbit aortic strips. The affinity for alpha-adrenoceptors was about 20 times greater than that for 5-HT-receptors. High concentrations of ACC-7513 did not block histamine in rabbit aortic strips, or beta 1- or beta 2-adrenoceptor responses induced by isoprenaline in guinea-pig right atria and trachea, respectively, but did block cholinoceptor responses induced by carbachol in rat uterus, non-competitively. High concentrations of ACC-7513 also produced sino-atrial depression in guinea-pig right atria and direct relaxation of depolarized rabbit aortic strips. ACC-7513 depressed blood pressure of conscious SHRs and produced a reflex increase in heart rate. The reductions in pressure were modest and of short duration. It is concluded that: (a) ACC-7513 is a potent, selective alpha-adrenoceptor and 5-HT receptor antagonist; and (b) ACC-7513 is not likely to be useful in the treatment of hypertension.
Anderson
W G
WG
Kam
S T
ST
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C045367:ACC 7513