Endorphin ligand

Substances with a neuromodulatory effect on brain neurotransmitters by direct actions of specific receptors that modify the actions of the transmitters listed include prostaglandins, adenosine, enkephalins, substance P, cholecystokinin, endorphins, endogenous benzodiazepine receptor ligands, and possibly histamine. CNS, central nervous system. NMDA, N-methyl-D-aspartate. Strych, strychnine. 

Shippenberg TS, Herz A Influence of chronic lithium treatment upon the motivational effects of opioids alteration in the effects of mu- but not kappa-opioid receptor ligands. J Pharmacol Exp Ther 256 1101-1106, 1991 Shippenberg TS, Millan MJ, Mucha RE, et al Involvement of beta-endorphin and mu-opioid receptors in mediating the aversive effect of lithium in the rat. Eur J Pharmacol 154 135-144, 1988... 

Today, we know that there are three types of opioid receptors—mu, delta, and kappa receptors [see review 3]. Proenkephalin contains six copies of Met-enkephalins and one copy of Leu-enkephalin. Enkephalins, especially Leu-enkephalin, are believed to be selective to delta receptors. Opiomelano-cortin contains (3-endorphin that has the Met-enkephalin at its amino terminus. (3-Endorphin is a nonselective ligand for mu and delta receptors. 

In addition to known antidepressants increasing endogenous opioids, opioid ligands have also been administered to depressed patients to determine if opioid compounds have clinical efficacy to treat depression. The opioid ligand cyclazocine improved symptoms in severely depressed, chronically ill mental patients in an open clinical trial and in clinical trials with patients unresponsive to the tricyclic antidepressant imipramine [16]. Intravenous (5-endorphin infusions improved mood in depressed patients in open case studies [17] and in depressed patients in a double-blind placebo-controlled study [18,19]. However, one study found a trend to improve depression scores in patients after acute and chronic (5-endorphin infusions, but it was not significant [20]. 

Belief in the existence of yet another variety of opioid receptor, designated e, is gaining ground.(228,240) This species was originally postulated to account for the unique characteristics of opioid receptors in the rat vas deferens.<229) /VEndorphin is a potent agonist in this tissue, but its effects do not appear to be mediated at /a-, k-, or 5-sites. Specific benzomorphan sites in rat brain membranes have been described that also do not seem to be of the /c-variety/230 and since /3h-endorphin is likewise a potent ligand for these sites,<231) they may well correspond to the putative e-receptors. 

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