Medgett I C
Neuropharmacology. 1985 May;24(5):381-90. doi: 10.1016/0028-3908(85)90022-x.
alpha-Adrenoceptors mediating inhibition of release of acetylcholine in the superior cervical ganglia of the rat have previously been characterized as of the alpha 2-subtype (Brown and Caulfield, 1981). In the present study, the effects of clonidine (2,6-dichlorophenylimino-2-imidazolidine), the 2,3- 2,4- and 2,5-dichloro isomers (St 476, St 363 and St 475) and the 3,4-dihydroxy analogue (DPI) were examined on transmission in this tissue. Compound action potentials (CAP; supramaximal preganglionic stimulation at 0.2 Hz) were recorded extracellularly. Clonidine, DPI and adrenaline inhibited the compound action potential; concentration-response curves were shifted to the right by phentolamine. The maximum inhibition of the compound action potential was similar for epinephrine and DPI. However, for clonidine a secondary inhibitory component, leading to almost complete blockade of the compound action potential, was seen in concentrations greater than 10 microM; similar effects were seen for the lipid-soluble analogues St 476, St 363 and St 475, suggesting a non-specific effect. In smaller concentrations, St 476, St 363 and St 475 exerted only weak inhibition of the CAP; St 363 and St 475 actually increased the height of the compound action potential, in a similar manner to phentolamine (0.1-3 microM), and all three analogues blocked the inhibitory effects of adrenaline. These latter data suggest partial agonist actions for St 476, St 363 and St 475. The rank order of inhibitory effectiveness (clonidine greater than St 476 greater than St 363 greater than St 475) parallels that for acute hypotensive effects in rats (Timmermans and van Zwieten, 1977a). The results suggest that sympatho-inhibitory effects of some imidazolidines may not result solely from activation of presynaptic alpha 2-adrenoceptors.
介导大鼠颈上神经节中乙酰胆碱释放抑制作用的α-肾上腺素受体先前已被鉴定为α2亚型（布朗和考尔菲尔德，1981年）。在本研究中，研究了可乐定（2,6-二氯苯基亚氨基-2-咪唑烷）、2,3-、2,4-和2,5-二氯异构体（St 476、St 363和St 475）以及3,4-二羟基类似物（DPI）对该组织中神经传递的影响。细胞外记录复合动作电位（CAP；0.2 Hz的超强节前刺激）。可乐定、DPI和肾上腺素抑制复合动作电位；酚妥拉明使浓度-反应曲线右移。肾上腺素和DPI对复合动作电位的最大抑制作用相似。然而，对于可乐定，在浓度大于10 microM时可观察到第二个抑制成分，导致复合动作电位几乎完全被阻断；脂溶性类似物St 476、St 363和St 475也有类似作用，提示存在非特异性效应。在较低浓度下，St 476、St 363和St 475对CAP仅产生微弱抑制；St 363和St 475实际上增加了复合动作电位的幅度，类似于酚妥拉明（0.1 - 3 microM），且这三种类似物均阻断了肾上腺素的抑制作用。这些数据表明St 476、St 363和St 475具有部分激动剂作用。抑制效力的顺序（可乐定＞St 476＞St 363＞St 475）与大鼠急性降压作用的顺序相似（蒂默曼斯和范·兹维滕，1977a）。结果表明，一些咪唑烷的交感抑制作用可能并非仅由突触前α2-肾上腺素受体的激活所致。
