Failure of selective antagonists (CH-38083 and idazoxan) to distinguish between prejunctional and postjunctional alpha 2-adrenoreceptors.

1. The prejunctional alpha 2-adrenoreceptor antagonist activity of CH-38083 (7,8-(methylenedioxi)-14-alpha-hydroxyalloberbane HCl), idazoxan and prazosin was determined against B-HT 920 on the tachycardia induced by cardiac nerve stimulation in pithed rats. Antagonism of cirazoline and B-HT 920 pressor responses was used to assess postjunctional alpha 1- and alpha 2-adrenoreceptor antagonist activities. 2. CH-38083 was more potent than idazoxan in blocking pre- and postjunctional alpha 2-adrenoreceptor sites. There was no difference between the activities of the two selective alpha 2-adrenoreceptor blocking agents on pre- and postjunctional alpha 2-adrenoreceptors. 3. These data classify CH-38083 as a potent and highly selective alpha 2-adrenoreceptor antagonist in vivo and further support evidence of the homogeneity of pre- and postjunctional alpha 2-adrenoreceptors.