Morphine opioid receptor antagonists

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]). 

Somatostatin and its analogues have been reported to be OP3 ( i) opioid receptor antagonists (57). Somatostatin infusions significantly reduced the effectiveness of morphine analgesia in a case report of three patients with cancer. 

Contrary to its 6-isomer (79) morphine-y3-3-glucuronide is not an analgesic but it is a potent /r-opioid receptor antagonist. The 3-glucuronide also resembles morphine in that it cau-... 

Opiates, narcotic compounds extracted or derived from opium, are a remarkable source of lead compounds for their potent pharmaceutical effects such as analgesics, antitussives and ataractics, and of which many synthetic derivatives have been prepared [8, 72], Apomorphine (28), a dopamine agonist derivative from morphine (5) but without analgesic properties like morphine, was recently approved as a therapy for Parkinson s disease [73], Hydrocodone (30) is a narcotic agent derived from thebaine (29) and is commonly combined with other analgesics such as acetaminophen and ibuprofen as drugs to relieve pain. [74]. Naloxone (31) and naltrexone (32) are both opioid receptor antagonists. Naloxone is used as a treatment for opioid... 

The substitution of an allyl moiety for the methyl group on the nitrogen atom of morphine produced the opioid receptor antagonists, nalorphine and naloxone (Fig. 14.15). 

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. 

The existence of further alternative transcripts of MOP was postulated by the observation that in knockout mice with disrupted exon 1, heroin but not morphine was still analgesically active. Based on earlier observations that the antagonist naloxazone blocked morphine-induced antinociception but not morphine-induced respiratory depression, a subdivision of the MOP in pi and p2 was proposed. However, no discrete mRNA for each of these MOP subtypes has been found. It is, however, possible that subtypes of MOPs result from heterodimerization with other opioid receptors or by interaction with other proteins. 

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