The alkylating prazosin analog SZL 49 inactivates both alpha 1A- 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 microM) 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.
Mante
S
S
Department of Pharmacology, Emory University Medical School, Atlanta, GA 30322.
Minneman
K P
KP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008566:Membranes / Q000648:ultrastructure; D010627:Phenethylamines / Q000378:metabolism; D011224:Prazosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D044024:Tetralones
D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; C051307:SZL 49; C051731:chlorethylclonidine; C010652:BE 2254; D003000:Clonidine; D011224:Prazosin