Sgd 101/75: a sympathomimetic that can be used to identify a new subtype of alpha-adrenoceptor, the alpha 1s-adrenoceptor.
When Sgd 101/75 was compared with clonidine in a number of tests for CNS activity, Sgd 101/75 exhibited little activity in any test. Sgd 101/75 raised BP without affecting HR in several species of anaesthetised animals. The rise in BP was subject to tachyphylaxis, could be antagonised by alpha 1-adrenoceptor antagonists, and was obtainable in reserpinised animals. The vasopressor effect of NA was antagonised by Sgd 101/75. Thus Sgd 101/75 is a directly acting partial agonist for vascular alpha 1-adrenoceptors. On the coaxially stimulated guinea-pig ileum and field stimulated rat vas deferens, the twitch response to single pulse stimulation was reduced by NA or clonidine stimulating prejunctional alpha 2-adrenoceptors. Sgd 101/75 antagonised these inhibitory effects competitively (pA2 for antagonism of clonidine on the vas = 6.12). Sgd 101/75 acted as a specific partial agonist on the alpha 1-adrenoceptors of the guinea-pig taenia caecum that subserve relaxation of this tissue. Sgd 101/75 was a full agonist on the alpha 1-adrenoceptors of the rat anococcygeus in vitro. Phenoxybenzamine (300 pM for 30 min, followed by 20 washes over the next 30 min) reduced contractions of the anococcygeus to Sgd 101/75, but produced little inhibition of NA-induced contractions. In phenoxybenzamine-pretreated preparations, Sgd 101/75 (400 microM) did not antagonise NA (maximal effect and EC50 values not changed significantly), so it was concluded that Sgd 101/75 and NA interact with different alpha 1-adrenoceptor subtypes in this tissue. The subtype specifically activated by Sgd 101/75 was designated the alpha 1s-adrenoceptor. The mouse anococcygeus contained alpha 1s-adrenoceptors, whereas this receptor was absent from the rabbit anococcygeus.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects*; D013566:Sympathomimetics
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; D010643:Phenoxybenzamine; D003000:Clonidine; C034204:indanidine; D009638:Norepinephrine