A water-soluble derivative of prazosin prazosinamine hydrochloride [1-(4'-amino-6',7'-dimethoxyquinazolin-2'-yl)-4-(6''-aminohexanoyl) piperazine hydrochloride], reversibly inhibits the calcium-mobilizing action of alpha 1-adrenergic agonists in the perfused rat liver.
A newly-synthesized derivative of prazosin, prazosinamine hydrochloride, was examined for its ability to antagonize the interaction of the alpha 1-adrenergic agonist phenylephrine with liver cells. Using a Ca2--selective electrode to measure changes in perfusate Ca2+ concentration, prazosinamine was found to be as effective as prazosin in inhibiting the phenylephrine-induced efflux of Ca2+ from the perfused liver. Maximal and half-maximal inhibition occurred at 150 nM and 25 nM prazosinamine, respectively. Prazosinamine appears to share the alpha 1-specificity of prazosin, but has other unique and desirable properties. Its solubility in aqueous media is about three orders of magnitude higher than that of prazosin. Also, its antagonistic effects are rapid in onset, and are reversed within seconds of terminating its infusion into the liver. These attributes seem to make this agent more useful than prazosin for adrenergic receptor studies in perfused tissues. The molecule can also be readily coupled to other ligands.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
C052522:prazosinamine; D010656:Phenylephrine; D002118:Calcium; D011224:Prazosin