Opiate antagonists side effects

Meptazinol hydrochloride is an injectable narcotic analgesic with antagonist properties it is similar in potency to meperidine. Meptazinol appeaurs to have a low propensity toward respiratory depression and other opiate-like side effects, possibly due to selective interaction with the mu-1 receptor. Also somewhat imique for an analgesic, it interacts with central cholinergic receptors. An oral form of meptazinol is under development. 

Another agent of this general type is nalmefene (47) Despite their useful characteristics, opiates display tolerance, addiction, abuse, and some toxic side effects Antagonists combat some of these effects, most notably respiratory depression and addiction Nalmefene reputedly has significant oral activity as a narcotic antagonist The synthesis of nalmefine concludes by Wittig olefination of naltrexone (46) to nalmefene (47) This molecular transformation resulted in a significant increase in oral potency as well (141... 

Opioid antagonists (Table 7.4), predominantly naloxone, are used clinically to reverse the effects of opiates in overdose or postoperative sedation. Naltrexone, which has oral bioavailability, is used for the treatment of narcotic addiction and alcohol dependence. As discussed below (Section 2.2.2.1), peripherally selective antagonists are being evaluated for treatment of constipation and other gastrointestinal side effects associated with opioid agonist use. 

There is now a search going on for orally active opiate structures which can act as antagonists at the p, receptor, agonists at the k receptor, and have no activity at the a receptor. Some success has been obtained, especially with the compounds shown in Fig. 12.34, but even these compounds still suffer from certain side-effects, or lack the desired oral activity. 

TREATMENT OF OPIOID OVERDOSAGE Naloxone hydrochloride should be used cautiously for opiate overdose because it also can precipitate withdrawal in dependent subjects and cause undesirable cardiovascular side effects. By carefully titrating the dose of naloxone, it usually is possible to antagonize the respiratory-depressant actions without eliciting a full withdrawal syndrome. The duration of action of naloxone is relatively short, and it often must be given repeatedly or by continuous infusion. Opioid antagonists also have been employed effectively to decrease neonatal respiratory depression secondary to the intravenous or intramuscular administration of opioids to the mother. In the neonate, the initial dose is 10 /ig/kg given intravenously, intramuscularly, or subcutaneously. 

Studied a series of opiate antagonists based upon a 6,7-benzomorphan nucleus (3). One of these compounds, pentazocine (4), proved to be a useful analgesic agent since it was largely devoid of the psychotomimetic side-effects often elicited by other benzomorphans, yet it retained analgesic activity equivalent in potency to about half of that of morphine [17], with minimum addiction liability in man [18]. 

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