Morphine receptor

Narcotic analgesic. A drug that alleviates pain by interacting with the morphine receptor. 

The identification of the morphine receptor spurred an effort in many laboratories to find an endogenous agonist for which that receptor was normally intended. Ultimately, a pair of pentapeptides that bound quite tightly to opiate receptors were isolated from mammalian brains. These peptides, called enkephalins (2, 3), show many of the activities of synthetic opiates in isolated organ systems. They do in fact show analgesic activity when injected directly into the brain. It is thought that lack of activity by other routes of administration is due to their rapid inactivation by peptide cleaving enzymes. 

In the above discussion on the mu/kappa receptor selectivity of the U-50488 (5) series, the steric properties of the tertiary amine and the distance between the amide and the aromatic ring were cited as important factors. This has been exploited by the Upjohn company to give the arylformamide-dimethyl-amine derivative (52) which is an analgesic in the mouse tail flick test (ED50 = 0.2 mg/kg s.c.) and causes mu-opioid like side-effects such as Straub tail, arched back and increased locomotor activity [81]. These behavioural effects and the association constant for the morphine receptor of compound... 

Klee WA, Nirenberg M. A neuroblastoma times glioma hybrid cell line with morphine receptors. Proc Natl Acad Sci USA 1974 71 3474-3477. 

Sharma SK, Nirenberg M, Klee WA. Morphine receptors as regulators of adenylate cyclase activity. Proc Natl Acad Sci USA 1975 72 590-594. 

A ketonic function at C-l may afford, dependent upon other substituents, analgesics that neither precipitate nor depress an opiate abstinence response. Ketocyclazocine(213) is an example of such a compound that is believed to act at k receptors rather than the usual morphine receptors. These will be discussed later in Chapter 12 (p. 405). 

In 1981 Portoghese(32) proposed the existence of two aromatic ring binding sites on the morphine -receptor. These may be the individual recognition sites for the tyrosine (T) and phenylalanine (P) moieties of the endogenous... 

Chem. < Ittd. London) 1962, 1577. NMR data indicates 22% eclipsed conformation which appears to enhance stereoselectivity for morphine receptors T. Sasaki et ah. J. Med. Chem. 9, 847 (1966). Pharmacology H. Nakamura, M. 

Recently, the endogenous morphine receptor ligand, enkephalin, has been iso= lated [305], identified chemically [306], and found to possess antinociceptive activity in mice after ICV injection [307], The interactions of the amines, enkephalin, and the cyclic nucleotides remain to be determined, and the scope for future studies of the mechanisms of action of the opiate analgesics becomes much wider as a result of these more recent studies. 

Fio. 24 Basic structure of morphine-like analgesics and modified form of model of the morphine-receptor. (Beckett. A. H. and Casy. A. F.. 1954.)... 

Atropine has shown a great efficacy against diarrhoea, especially when combined with a morphine receptor agonist. The commercial combination Lomotil (atropine sulphate 0.025 mg/dephenoxylate. HCl 2.5 mg) is one of the best treatments for diarrhoea. However, atropine in this case is used to produce some side effects which will discourage the abuse of diphenoxylate. 

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