Opiate functional property

Changing the amino acid sequence of the cloned receptors by mutating nucleotides within the receptor cDNAs has proven to be an effective mechanism by which to identify structural features of the receptors responsible for their unique functional properties. In particular, site-directed mutagenesis has been employed to determine the ligand binding domains of each opiate receptor. 

Careful analyses of the pharmacologic properties of 3H-hailucinogen binding sites indicated that they may correspond to 5-HT receptors (in the case of 3H-LSD), sigma opiate receptors (in the case of 3H-PCP), or even GABA receptors (in the case of 3H-muscimol). Such data recall that hallucinogens should interfere markedly with the metabolism of neurotransmitters in the CNS. These hallucinogen-induced alterations of neurotransmitter metabolism and functions are summarized below. 

Alkaloids such as boldine, codeine, narceine and morphine are active factors in their receptors. Boldine has morphine-like properties and is active on opioid receptors. It may be used to treat stomach disorders and as metabolic stimulant. As it is similar to morphine, boldine can also be considered in the possible development of treatments for narcotic dependence. Codeine also binds to opiate receptors, and specifically functions to reduce bronchial secretions. Codeine can also be used as a cough suppressant when acting on the centre of the medulla oblongata and as a sedative agent. 

Opioid receptors are present in human T-cell lymphocytes (Wybran et al., 1979), which may provide a link between the central nervous system and the immune system. There is a considerable body of literature, which demonstrates a modulatory function of the immune system by opioids. Opioids alter the biochemical and proliferative properties of various cellular components of the immune system (Webster, 1998). (3-Casomorphins affect the human mucosal immune system, possibly via the opiate receptor, since the opiate receptor antagonist, naloxone, reverses the activity (Elitsur et al., 1991). P-Casomorphins and a-casein exorphins inhibit the cell proliferation of human prostate cell lines by a mechanism partly involving opioid receptors (Kampa et al., 1997). 

Opiates are reported to influence GI function in two ways first, they affect smooth muscle, which reduces the transit time, and second, they affect the intestinal transport of electrolytes, which explains their antisecretory properties (Wiister et al., 1981). 

Difenoxin, an opiate receptor agonist with antidiarrheal properties (2 mg p.o.), is indicated as an adjunctive treatment of acute nonspeciflc exacerbations of chronic functional diarrhea. 

Diphenoxylate is an opiate (schedule V) with antidiarrheal properties. It is usually dispensed with atropine and sold as Lomotil. The atropine is added to discourage the abuse of diphenoxylate by narcotic addicts who are tolerant to massive doses of narcotic but not to the CNS stimulant effects of atropine. Diphenoxylate shonld be used cautiously in patients with obstructive jaundice because of its potential for hepatic coma, and in patients with diarrhea cansed by pseudomembranous colitis because of its potential for toxic megacolon. In addition, it should be used cautiously in the treatment of diarrhea caused by poisoning or by infection by Shigella, Salmonella, and some strains of E. coli because expulsion of intestinal contents may be a protective mechanism. Diphenoxylate should be used with extreme caution in patients with impaired hepatic function, cirrhosis, advanced hepatorenal disease, or abnormal liver function test results, because the drug may precipitate hepatic coma. Because diphenoxylate is structurally related to meperidine, it may cause hypertension when combined with monoamine oxidase inhibitors. As a narcotic, it will augment the CNS depressant effects of alcohol, hypnotic-sedatives, and numerous other drugs, such as neuroleptics or antidepressants that cause sedation. 

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