THE ALKYLATING PRAZOSIN ANALOG SZL-49 INACTIVATES BOTH ALPHA-1A-ADRENOCEPTORS AND ALPHA-1B-ADRENOCEPTORS

A chemically reactive prazosin analog (SZL) 49) has been suggested to be an alpha-1A-selective alkylating agent. We found SZL 49 competed for alpha-1-adrenoceptor binding sites with a similar potency (IC50 1 nM) in tissues enriched in both the alpha-1A (hippocampus) and alpha-1B (liver) subtypes. SZL 49 was very difficult to wash out of membrane preparations. However, pretreatment with a high concentration of SZL 49 (0.1-mu-M) followed by multiple washings resulted in a similar 40-50% loss of alpha-1-adrenoceptor binding sites in both liver and hippocampus. Pretreatment of hippocampal membranes with both SZL and the alpha-1B-selective alkylating agent chloroethylclonidine, sequentially or in combination, caused only a slightly greater inactivation than did either drug alone. Analysis of WB 4101 inhibition curves showed that pretreatment of hippocampal membranes with SZL 49 did not alter the proportions of alpha-1A- and alpha-1B-adrenoceptor subtypes. These data suggest that SZL 49 does not demonstrate in vitro selectivity for either the alpha-1A- or alpha-1B-receptor subtypes.