抄録
The effects of 8 imidazoline derivatives on pre- and postsynaptic α-adrenoceptors and [3H] norepinephrine release were investigated in the rat vas deferens and were compared with those of reference drugs, yohimbine, phentolamine, tolazoline, and prazosin. K-6341 and K-6343 activated postsynaptic α1-adrenoceptor and were antagonized by prazosin. The order of potency series as α1-antagonist, prazosin > phentolamine > yohimbine > K-4011 > K-3827 > K-4300, tolazoline was found in antagonism against phenylephrine. Many derivatives exhibited an antagonistic action against clonidine, and the potency series as α2-antagonist was revealed as follows : phentolamine > yohimbine > K-3827 > K-4011 > K-6341 > K-6343 > K-4300, tolazoline > prazosin > K-4299. The antagonistic effect was more selective on presynaptic (α2) than postsynaptic (α1) adrenoceptor and the rank order of selectivity (KB-post/KB-pre) was K-3827 > yohimbine > K-4011 > tolazoline, K-4300 > phentolamine > prazosin. Imidazoline derivative increased [3H]norepinephrine release, the actions of K-3827, K-6341 and K-4300 being particularly potent. From these results, the structure-activity relationship was summarized. First, when 2', 3'-methylenedioxyphenyl group is connected with the imidazoline ring via an amino or methylene residue, these compounds become α1-agonist. Secondly, when the methylenedioxyphenyl group and the imidazoline ring are connected via an amino residue, these compounds show a weak agonistic and potent antagonistic characteristics at the presynaptic α2-adrenoceptor. Thirdly, an addition of a methylenedioxy radical to the phenyl ring increased the affinity of the compounds to presynaptic α2-receptor.
