Naltrexone pharmacology

Opiates iateract with three principal classes of opioid GPCRs )J.-selective for the endorphiQS,5-selective for enkephalins, and K-selective for dynorphias (51). AU. three receptors have been cloned. Each inhibits adenylate cyclase, can activate potassium channels, and inhibit A/-type calcium channels. The classical opiates, morphine and its antagonists naloxone (144) and naltrexone (145), have moderate selectivity for the. -receptor. Pharmacological evidence suggests that there are two subtypes of the. -receptor and three subtypes each of the 5- and K-receptor. An s-opiate receptor may also exist. 

Littleton J, Zieglgansberger W Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence. Am J Addict 12 (suppl 1) S3-S11,2003... 

Kleber HD Ultrarapid opiate detoxification. Addiction 93 1629-1633, 1998 Kleber HD, Kosten TR Naltrexone induction psychologic and pharmacologic strategies. J Clin Psychiatry 43 29-38, 1984... 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Pharmacology Nalmefene, an opioid antagonist, is a 6-methylene analog of naltrexone. Nalmefene prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Nalmefene has no opioid agonist activity it does not produce respiratory depression, psychotomimetic effects or pupillary constriction, and no pharmacological activity was observed when it was administered in the absence of opioid agonists. Nalmefene can produce acute withdrawal symptoms in individuals who are opioid-dependent. 

Pharmacology Naltrexone is a pure opioid antagonist. It markedly attenuates or completely blocks, reversibly, the subjective effects of IV administered opioids. 

Brewer C (1996). On the specific effectiveness, and under-valuing, of pharmacological treatments for addiction a comparison of methadone, naltrexone and disulfiram with psychosocial interventions. Addiction Research, 3, 297-313... 

Naltrexone and nalmefene are structurally related to naloxone. Naltrexone is the /V-cyclopropy I methyl analogue of oxymorphone while nalmefene is the /V-allyl analogue. They have similar pharmacological properties to naloxone but with longer durations of action, with elimination half-lives in excess of 8 hours. They also have significant oral availability. They are used mainly in the management of addicts. 

The biggest challenge is the treatment of addiction itself. Several approaches have been proposed, but all remain experimental. One approach is to pharmacologically reduce cravings. The P-opioid receptor antagonist and partial agonist naltrexone is FDA-approved for this indication in opioid and alcohol addiction. Its effect is modest and may involve a modulation of endogenous opioid systems. 

With the exceptions of methadone maintenance, LAAM maintenance, and nicotine substitution therapy (and probably naltrexone for alcohol addiction and bupropion for nicotine addiction), no clearly effective pharmacotherapy for drug addiction exists. Certainly, no broadly effective pharmacotherapy exists (effective for addictions to drugs of different chemical classes and pharmacological categories). Therapeutic strategies based on psychotherapy, group therapy, behavior modification, economic incentives, and aversion deconditioning have proven limited. 

To review the pharmacology of alcohol, and agents to reduce alcohol consumption including acamprosate and naltrexone. 

The main metabolite (> 70%) of naltrexone biotransformation in man is 6/ -naltrexol [39] which is pharmacologically active as an opioid antagonist. 

An examination 313 of the importance of C-6 chirality on the binding and pharmacological actions of naltrexone-derived receptor affinity labels was made possible by the accessibility of both 6a-naltrexamine (193) and 6/3-naltrexamine (i92). 306,299) These amines themselves possessed antagonist activity in mice with a prolonged duration of action. 299 ... 

All of these series have pharmacological actions that parallel those of morphine, including dependence liability. They produce complete suppression of the abstinence syndrome in morphine-dependent monkeys, and their effects may be reversed by naltrexone. 

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