Structure and biological activity of (-)-[3H]dihydroalprenolol, a radioligand for studies of beta-adrenergic receptors.
(-)-Alprenolol is a potent competitive beta-adrenergic antagonist. "(-)-[3H]Alprenolol", a radioactive form of this agent produced by catalytic reduction with tritium, has recently been used successfully as a radioligand for direct studies of beta-adrenergic receptors. In this communication it is documented that the compound formed by catalytic reduction of (-)-alprenolol with tritium gas is the saturated product (-)-[3H]dihydroalprenolol in which tritium is added across the double bond and exchanged into the adjacent benzylic position. No exchange into the aromatic ring was observed. These conclusions were substantiated by results obtained on hydrogenation and deuteration of (-)-alprenolol. The biological activity of (-)-[3H]dihydroalprenolol, dihydroalprenolol, and alprenolol was also shown to be identical as assessed by direct ligand binding and inhibition of catecholamine-stimulated adenylate cyclase.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000097:blood; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001001:Anura; D055598:Chemical Phenomena; D002621:Chemistry; D004910:Erythrocyte Membrane / Q000201:enzymology / Q000378:metabolism; D006865:Hydrogenation; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014316:Tritium
D000067956:Adenylyl Cyclase Inhibitors; D008024:Ligands; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D000526:Alprenolol; D000262:Adenylyl Cyclases