Weetman D F, Jahn U, Ismail S, Chadwick M A, Coates J, Lawson K, Turner N, Thiele K
Methods Find Exp Clin Pharmacol. 1983 Sep;5(7):425-34.
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.
在多项中枢神经系统活性测试中，将Sgd 101/75与可乐定进行比较时，Sgd 101/75在任何测试中均表现出微弱活性。在几种麻醉动物中，Sgd 101/75可升高血压而不影响心率。血压升高会出现快速耐受性，可被α1肾上腺素能受体拮抗剂拮抗，且在利血平化的动物中也可出现。Sgd 101/75可拮抗去甲肾上腺素的升压作用。因此，Sgd 101/75是血管α1肾上腺素能受体的直接作用部分激动剂。在同轴刺激的豚鼠回肠和场刺激的大鼠输精管上，去甲肾上腺素或可乐定刺激突触前α2肾上腺素能受体可降低对单脉冲刺激的抽搐反应。Sgd 101/75竞争性拮抗这些抑制作用（可乐定对输精管拮抗作用的pA2 = 6.12）。Sgd 101/75在豚鼠盲肠带的α1肾上腺素能受体上作为特异性部分激动剂发挥作用，该受体可使该组织舒张。Sgd 101/75在体外对大鼠肛门尾骨肌的α1肾上腺素能受体是完全激动剂。酚苄明（300 pM作用30分钟，随后在接下来的30分钟内冲洗20次）可降低肛门尾骨肌对Sgd 101/75的收缩反应，但对去甲肾上腺素诱导的收缩几乎没有抑制作用。在酚苄明预处理的制剂中，Sgd 101/75（400 microM）不拮抗去甲肾上腺素（最大效应和EC50值无明显变化），因此得出结论，Sgd 101/75和去甲肾上腺素在该组织中与不同的α1肾上腺素能受体亚型相互作用。被Sgd 101/75特异性激活的亚型被命名为α1s肾上腺素能受体。小鼠肛门尾骨肌含有α1s肾上腺素能受体，而兔肛门尾骨肌中不存在该受体。
