5-Opioid receptor antagonist

Naloxone (Narcan) and naltrexone hydrochloride (Trexan) reverse the respiratory depressant action of narcotics related to morphine, meperidine, and methadone. They differ from other narcotic analgesics in several respects. Naloxone does not cause respiratory depression, pupillary constriction, sedation, or analgesia. However, it does antagonize the actions of pentazocine. Naloxone neither antagonizes the respiratory depressant effects of barbiturates and other hypnotics nor aggravates their depressant effects on respiration. Similar to nalorphine, naloxone precipitates an abstinence syndrome when administered to patients addicted to opiate-like drugs. 

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Opiate overdose is a medical emergency that can result in respiratory and CNS depression. The opioid receptor antagonist naloxone immediately reverses cardiorespiratory depression. However, repeated naloxone administration is required, since the effects of naloxone last for 30 min, while opioid agonists can remain at potentially lethal blood levels for several hours. 

The pharmacological and/or adverse effects of a drug can be reversed by co-administration of drugs which compete for the same receptor. For example, an opioid receptor antagonist naloxone is used to reverse the effects of opiates. Drugs acting at the same site with opposite effects also can affect each other, e.g. the reduction in the anticoagulant effect of warfarin by vitamin K. 

Opioid systems in the brain are important for the reinforcing effects of ethanol. Selective p-opioid receptor antagonists reliably decrease ethanol drinking in rats. 

Opioid receptor antagonists have been found to modulate brain dopamine-mediated behavioral and cellular functions such as motor activity, drug selfadministration, and brain stimulation reward (Koob and Bloom 1988). 

Portoghese PS, Sultana M, Nagase H, Takemori AE. Application of the message-address concept in the design of highly potent and selective nonpeptide 6 opioid receptor antagonists. J Med Chem 1988 31 281-282. 

Portoghese PS, Nagase H, Maloney Huss KE, Lin CE, Takemori AE. Role of spacer and address components in peptidomimetic 6 opioid receptor antagonists related to naltrindole. J Med Chem 1991 34 1715-1720. 

Schiller PW, Weltrowska G, Nguyen TM-D, Wilkes BC, Chung NN, Lemieux C. TIPPpP] a highly potent and stable pseudopeptide opioid receptor antagonist with extraordinary selectivity. J Med Chem 1993 36 3182-3187. 

Page D, McClory A, Mischki T, Schmidt R, Butterworth J, St-Onge S, Labarre M, Payza K, Brown W. Novel Dmt-Tic dipeptide analogues as selective delta-opioid receptor antagonists. Bioorg Med Chem Lett 2000 10 167-170. 

Arakawa K, Akami T, Okamoto M, Akioka K, Nakai I, Oka T, Nagase H. Immunosuppression by delta opioid receptor antagonist. Transplant Proc 1993 25 738-740. 

Portoghese P, Sultana M, Nagase H et al. A highly selective delta-1 opioid receptor antagonist 7-benzylidenenaltrexone. Eur J Pharmacol 1992 218 195-196. 

Based upon recent controlled studies, there is considerable evidence that opioids such as morphine induce substantial effects on immune status. For example, it has been shown that morphine administration is associated with alterations in a number of immune parameters, such as natural-killer cell activity [12,13], proliferation of lymphocytes, [13, 14] antibody production [15,16], and the production of interferon [17]. Studies in our laboratory have shown that acute morphine treatment in rats suppresses splenic lymphocyte proliferative responses to both T- and B-cell mitogens, splenic natural-killer cell activity, blood lymphocyte mitogenic responsiveness to T-cell mitogens, and the in vitro production of the cytokines interleukin-2 and interferon-y [18-22], Furthermore, the immune alterations induced by morphine are dose-dependent and antagonized by the opioid-receptor antagonist, naltrexone (e.g., [22]). 

Delta opioid receptor Antagonist analog Hydroxyphenyl piperidine 153... 

Devine DP, Leone P, Wise RA. (1993). Mesolimbic dopamine neurotransmission is increased by administration of mu-opioid receptor antagonists. EurJ Pharmacol. 243(1) 55-64. 

The use of structurally rigid DKPs as bioactive models for opioid receptor antagonists has been proposed. These compounds are used in the elucidation of the binding requirements and will lead to the design of highly selective molecules with potential clinical application for diseases of the opioid system. These include the treatment of autism, alcohol dependency, and modulation of immunity Further studies by Baures has... 

Guay DRP (2009) Methylnaltrexone methobromide The first peripherally active, centrally inactive opioid receptor-antagonist. Consult Pharm 24 210-226. 

Naltrexone, an orally active opioid receptor antagonist, restores erectile function in some patients with idiopathic ED. 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

Naltrexone, a relatively long-acting opioid receptor antagonist, blocks the effects at -opioid receptors (see Chapter 31). Studies in experimental animals first suggested a link between alcohol consumption and opioids. Injection of small amounts of opioids was followed by an increase in alcohol drinking, whereas administration of opioid antagonists inhibited self-administration of alcohol. 

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. 

Opioid receptor antagonists Alvimopan, methylnaltrexone block intestinal ii-opioid receptors but do not enter CNS, so analgesia is maintained... 

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