Antagonists of opioid receptors

The answer is c. (Hardman, p 546.) Pentazocine is a mixed agonist-antagonist of opioid receptors. When a partial agonist, such as pentazocine, displaces a full agonist, such as methadone, the receptor is less activated this leads to withdrawal syndrome in an opioid-dependent person. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

Naloxone Nonselective antagonist of opioid receptors Reverses the acute effects of opioids can precipitate severe abstinence syndrome Opioid overdose Effect much shorter than morphine (1-2 h), therefore several injections required... 

Naltrexone Antagonist of opioid receptors Blocks effects of illicit opioids Treatment of alcoholism Half-life 4h... 

Heterocycles as agonists and antagonists of opioid receptors 03JMC1775. 

Policyclic heterocycles as antagonists of opioid receptors 01JMC2259. 

It is universally accepted that the action of opioids is mediated by specific receptors. It is presumed that several types of opioid receptors exist p, k, 5, and a. A few of these are in turn subdivided into subtypes. It has been found that opioid receptors are seven transmembrane G-protein-coupled receptors that are localized in the membranous part of the synaptosomal head it has also been found that they are glycoproteins. They are prone to conformational changes in certain situations, which is essential for their selective binding with agonists or antagonists. 

The efficacy and strength of opioid antagonists varies depending on the type of opioid receptors (u-, 8-, K-, a-) with which they interact. The mechanism of their action is not fully clear. However, it has been suggested that they antagonize the action of endogenous opioid peptides. 

Nalorphine and levallorphan are examples. For example in patients with postoperative pain the analgesic effects of 10 mg of nalorphine is about the same as 10 mg of morphine. On the other hand naloxone and naltrexone seem to have no agonistic activity and some antagonistic affinity for all types of opioid receptors. Although antagonists could be expected to have effects by altering the actions of endogenous opioid peptides mostly such effects are not discernable. 

Flupirtine is both a nonspecific antagonist NMDA and an agonist of opioid receptors. This analgesic is prescribed for migraine. Neuroprotector effects in neurodegenerative diseases (Alzheimer and prion diseases) are being investigatived. ... 

Opioid receptor binding Pentazocine (Brogden et al., 1973) is a mixed opioid agonist-antagonist with agonistic effects at the kappa and partial antagonistic effects at the p-type of opioid receptor. 

In recent years there has been a major research effort, so far without success, to produce potent, centrally acting analgesics that do not have an abuse potential. The discovery of various types of opioid receptor, which may have different effects on central neurotransmitter function, may ultimately lead to the development of such a drug. In the meantime, the most widely used opioids, for example morphine, heroin (also called diacetylmorphine) and codeine are therapeutically effective but are liable to be abused and produce dependence. The structure of some of the morphine-like analgesics and their antagonists are shown in Figure 15.2. 

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