Takeuchi K, Akatsuka K, Kasuya Y
J Pharmacobiodyn. 1986 Apr;9(4):385-94. doi: 10.1248/bpb1978.9.385.
The effects of 8 imidazoline derivatives on alpha-adrenoceptor-mediated contraction or relaxation of various kinds of smooth muscle preparations were investigated. In rabbit aortic strips, K-6341, K-6343 and K-4011 produced alpha-agonistic action which was antagonized by prazosin. In the study of alpha-antagonistic action of imidazoline derivatives, i.e. antagonism against norepinephrine- or phenylephyrine-induced contraction of the rabbit aortic strip, the order of potency series, prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300 greater than tolazoline was found. Reserpine pretreatment did not affect the results. In the study of alpha-antagonistic effect on the relaxing response to norepinephrine of methacholine-contracted rat ileum, the potency series was revealed as follows: prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300, tolazoline. A similar experiment was performed on histamine-contracted guinea-pig taenia coli, and the results were nearly identical to the case of the rat ileum, except that K-6341 and K-6343 also exhibited alpha-antagonistic action which was not detected in the rat ileum. This suggests that alpha 2-receptor may exist in the postsynaptic alpha-adrenoceptor in the guinea-pig taenia coli. The results of the present study indicate that the potency of imidazoline derivatives to inhibit norepinephrine-induced contraction of some smooth muscle is almost identical to that which inhibited norepinephrine-induced relaxation of other smooth muscles. Furthermore, K-4300 was found to possess anti-acetylcholine and anti-histamine actions in the guinea-pig taenia coli and anti-serotonin action in the rat fundus strips.
研究了8种咪唑啉衍生物对α-肾上腺素受体介导的各种平滑肌制剂收缩或舒张的影响。在兔主动脉条中，K-6341、K-6343和K-4011产生α-激动作用，该作用可被哌唑嗪拮抗。在研究咪唑啉衍生物的α-拮抗作用，即对去甲肾上腺素或苯肾上腺素诱导的兔主动脉条收缩的拮抗作用时，发现效价顺序为：哌唑嗪＞酚妥拉明＞育亨宾＞K-4011、K-3827、K-4300＞妥拉唑啉。利血平预处理不影响结果。在研究对乙酰甲胆碱收缩的大鼠回肠对去甲肾上腺素舒张反应的α-拮抗作用时，效价顺序如下：哌唑嗪＞酚妥拉明＞育亨宾＞K-4011、K-3827、K-4300、妥拉唑啉。对组胺收缩的豚鼠结肠带进行了类似实验，结果与大鼠回肠的情况几乎相同，只是K-6341和K-6343也表现出α-拮抗作用，而在大鼠回肠中未检测到。这表明豚鼠结肠带的突触后α-肾上腺素受体中可能存在α2-受体。本研究结果表明，咪唑啉衍生物抑制去甲肾上腺素诱导的某些平滑肌收缩的效力与抑制去甲肾上腺素诱导的其他平滑肌舒张的效力几乎相同。此外，发现K-4300在豚鼠结肠带中具有抗乙酰胆碱和抗组胺作用，在大鼠胃底条中具有抗5-羟色胺作用。
