The present review focuses on the hypothesized D1/D2 dopamine (DA) receptor classification, originally based on the form of receptor coupling to adenylate cyclase activity. The pharmacological effects of compounds exhibiting putative selective agonist or antagonist profiles at those DA receptors positively coupled to adenylate cyclase activity (D1 DA receptors) are extensively reviewed. Comparisons are made with the effects of putative selective D2 DA receptor agonists and antagonists, and on the basis of this work, the DA receptor classification is critically evaluated. A variety of biochemical, behavioral, and electrophysiological evidence is presented which supports the view that D1 and D2 DA receptors can interact in both an opposing and synergistic fashion. Particular attention is focused on the possibility that D1 receptor stimulation is required to enable the expression of certain D2 receptor-mediated effects, and the functional consequences of this form of interaction are considered. A hypothetical model is presented which considers how both the opposing and enabling forms of interaction between D1 and D2 DA receptors can control behavioral expression. Finally, the clinical relevance of this work is discussed and the potential use of selective D1 receptor agonists and antagonists in the treatment of psychotic states and Parkinson's disease is considered.

D1 dopamine receptor--the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications.

Naltrindole, a highly selective and potent non-peptide δ opioid receptor antagonist

Binaltorphimine and nor-binaltorphimine, potent and selective k-opioid receptor antagonists

I Abbreviations used: ACTH, adrenocorticotropic hormone; ADCC, antibody-dependent cellular cytotoxicity; Bma .. total number of binding sites; BREM, bremazocine, an agonist with modest selectivity for K sites; CCK, cholecystokinin; ConA, concanavalin A; DADLE, [D-Ala2,D-LeuS]enkephalin, an agonist somewhat selective for /j �ites; DEX, dextrorphan, inert enantiomer of LEV; DHM, dihydromorphine, a Jl-selective agonist; DIP, dipre­ norphine, a relatively nonselective antagonist; DYN, dynorphin, a peptide product of the dynorphin gene, selective for K sites; EKC, ethylketazocine, a benzomorphan agonist with modest selectivity for K sites; END, endorphin; a peptide product of the pro-opio­ melanocortin gene; <Xand y-endorphin are fragments of fJ-endorphin; fJ-endorphin is selective for e sites; ETO, etorphine, a relatively nonselective agonist; fMLP, formyl-methio­ nyl-leucinyl-phenylalanine; granulo, granulocyte(s); h, human; ICso, concentration of a com­ peting ligand that reduces specific binding of radioligand by 50%; icv, intracerebro­ ventricular; IFN, interferon; ir-, immunoreactive; Kd, K;, equilibrium dissociation con­ stants, determined by binding isotherm or by competition, respectively; LENK, [Leu]en­ kephalin, a minor product of the pro-enkephalin gene, an agonist somewhat selective for {) sites; leuko, leukocyte(s); LEV, levorphanol, a Jl-selective agonist; Iympho, Iymphocyte(s); m, mouse; M.p, macrophage(s); MENK, [Met]enkephalin, major product of the pro-enkephalin gene, a /j-selective agonist; MNC, mononuclear cell(s); mono, monocyte(s); MOR, morphine, a Jl-selective agonist; NA, not applicable; NAL, naloxone, a moderately jl-selective antag­ onist; NK, natural killer; NR, not reported; NTX, naltrexone, a long-lasting Jl-selective antagonist closely related to naloxone; PBL, peripheral blood Iymphocyte(s); PBMNC, peripheral blood mononuclear cell(s); PHA, phytohemagglutinin; PMNL, polymorpho­ nuclear leukocyte(s); r, rat; RIA, radioimmunoassay; spleno, splenocyte; SRBC, sheep red blood cells; VIP, vasoactive intestinal peptide.

L. Miller

Papers

ICI 174864: A highly selective antagonist for the opioid Δ-receptor

Divergent structure activity relationships in series of enkephalin agonists and cognate antagonists.