Drug Receptors

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Most drugs interact with receptors (or enzymes) for which the natural ligand (or substrate) is known. There are, however, a number of receptors, distinct from the evolving class of orphan receptors, for which the synthesized drug is the only known ligand. The best example of this is the central benzodiazepine (BZ) receptor present on the GABAAion channel complex that was originally identified using radiolabeled diazepam (14). Because this is the site of action of the widely used BZ anxiolytic drug class, this is a bona fide receptor with clinical relevance. However, despite considerable efforts and a number of interesting candidate compounds, no endogenous li-gand has yet been unambiguously identified that would represent an endogenous modulator of anxiety acting through this site. Other examples of drug receptors are the cannabi-receptor family, comprised of two members, CB, and CB,, through which the following compounds act: A9-tetrahydrocannibol, the active ingredient of the psychoactive recreational drug/analgesic/antiemetic drug marijuana acts (95); the vanilloid receptor, VR-1, the known ligand for which is capsaicin, the ingredient in red pepper that evokes the sensation of heat (59); and the opioid receptor family (96), the site of action of morphine and other derivatives of the poppy. For each of these drug receptors, endogenous mammalian ligands, anandamide (95), the endovanilloid, N-arachidonyl-dopamine (NADA) (96) enkephalins (97), and orphanin/FQ (90) have been identified.

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