Methadone pharmacological properties

LAAM (L-a-acetylmethadol or levomethadyl acetate) is a full agonist at the i opioid receptor with pharmacologic properties similar to those of methadone. A number of studies have demonstrated that treatment with LAAM results in reduction of opioid use and beneficial effects comparable to those achieved with methadone (Ling et al. 1978 Tennant et al. 1986 Zangwell et al. 1986). However, retention rates are higher in patients who take methadone doses of 80—100 mg/day. 

Methadone is an MOR(OP3, i) receptor agonist with pharmacological properties similar to those of morphine. It is an attractive alternative MOR opioid receptor analgesic, because of its lack of neuroactive metabolites, a clearance that is independent of renal function, good oral systemic availability, a longer half-life with fewer doses needed per day, and extremely low cost. It is mainly metabolized by CYP3A4. 

Methadone Methadone was first synthesized as a morphine substitute and possesses many of that drag s pharmacological properties. It is mainly excreted in mine in imchanged form (5%-50% of a dose) or is metabolized by A-demethylation with spontaneoirs cycfization of the resirlting metabolite to 2-ethyfidene-l,5-dimethyl-3,3-dipher5flpyrrofidine (EDDP) (3%-25% of a dose). 

Another example of the largest common substructure search is shown in Fig. 6. Although they differ greatly in structure from one another, morphine, meperidine, and methadone exhibit similar pharmacological activities (analgesic properties). By the search with level (4) expression, two connected graphs are... 

Interest in dithienylalkanes of potential pharmacological importance was aroused by the discovery that some 3-dialkylamino-l,l-bis(2-thienyl)but-l-enes possess analgesic activity.116 Compounds 91, termed thiambutenes, are prepared by dehydration of carbinols of general formula 92. Considerable variations in the substituents have been made in the search for greater activity and for a reduction in undesirable side effects often, these variants have both analgesic and antitussive properties. Substances with obvious structural similarities to 91 and 92, namely, the thiophene analog of methadone (93) and of isomethadone, have also been prepared.63,107... 

PHARMACOLOGICAL ACTIONS The outstanding properties of methadone are its analgesic activity, its oral efficacy, extended duration of action in suppressing withdrawal symptoms in physically dependent individuals, and tendency to show persistent effects with repeated administration. Miotic and respiratory-depressant effects can be detected for >24 hours after a single dose, and on repeated administration, marked sedation is seen in some patients. Effects on cough, bowel motility, biliary tone, and the secretion of pituitary hormones are qualitatively similar to those of morphine. 

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