PK(I) VALUES OF PRAZOSIN AND IDAZOXAN FOR RECEPTORS STIMULATED BY NEURONALLY RELEASED TRANSMITTER IN THE EPIDIDYMAL PORTION OF RAT ISOLATEDVAS-DEFERENS

1 A new method has been used to measure pK(I) values of prazosin and i dazoxan against neuronally-released transmitter in the epididymal port ion of the rat isolated vas deferens. The most reproducible results we re obtained with a prolonged antagonist equilibration time (Ih). 2 Und er these conditions the pK(I) of prazosin was practically unaffected b y addition of alpha, beta-methylene-adenosine-5'-triphosphate (10 mu M ) to desensitize purinoceptors. Addition of desmethylimipramine (DMI) (0.3 mu M) produced a small, but statistically non-significant, reduct ion. 3 The same method has been used to measure the pK(I) of prazosin against exogenous noradrenaline. In the latter case addition of DMI (0 .3 mu M) and corticosterone (30 mu M) together produced a statisticall y significant reduction in the apparent pK(I) of prazosin. 4 The new m ethod for estimating pK(I) values shows that DMI itself acts either ps eudo-irreversibly or non-competitively and may be reducing the apparen t pK(I) of prazosin. 5 The pK(I) values obtained for prazosin and idaz oxan against neuronally-released transmitter are in good agreement wit h those obtained by other workers for the actions of these drugs on al pha-adrenoceptors.