Mu receptor antagonists

It is a strong kappa receptor agonist and mu receptor antagonist. Its agonistic property is approximately three to four times more than pentazocine and its antagonistic property is approximately 10 times more than pentazocine. It has less abuse liability in comparison to pentazocine. It is useful in postoperative pain, myocardial infarction and labour. 

Tortella FC, Robles L, Holaday JW. The anticonvulsant effects of DADL are primarily mediated by activation of delta opioid receptors interaction between delta and mu-receptor antagonists. Life Sci 1985 37 497-503. 

Mu-Receptor Antagonists Derived from Somatostatin. Potent p-opioid antagonists have been identified that are derivatives of somatostatin rather than of an opioid peptide (see Ref 656 for a review). Somatostatin exhibits low affinity for opioid receptors, and the potent somatostatin analog SMS-201,995 (D-Phe-cycZo[CyS Phe-D-Trp-Lys-Thr-Cys]-Thr-ol) was found to be an antagonist at p, opioid receptors (940). Further structural modification yielded a series of peptides with the general structure D-Phe-cycZo[Cys-Tyr-D-Trp-X-Thr-Pen]-ThrNH, where X = Lys, Om, or Arg in CTP, CTOP (19, Fig. 7.4), and... 

Naloxone Opioid mu receptor antagonist used to reverse CNS depressant effects of... 

There are now selective antagonists for all three opiate receptors (see Table 21.2) but with the exception of naloxone they are experimental tools for probing the functional roles of the opiate receptors. Naloxone is a potent competitive antagonist at all three receptors with highest affinity for the mu receptor. It will rapidly reverse all opiate... 

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. 

Buprenorphine is derived from thebaine. It is a partial mu agonist with kappa antagonist activity. Buprenorphine has 25 to 50 times the potency of morphine. It is used to produce a longer-lasting analgesia than morphine. Effects of buprenorphine last longer because it is released more slowly from mu receptors than morphine. It is available as an injectable for intramuscular (IM) or intravenous administration in a 1-ml solution containing 0.3 mg buprenorphine (as buprenorphine HC1) for the relief of moderate to severe pain. It is also available to treat opioid dependence in the formulation of a tablet,51 alone or in combination with naloxone, in 2- or 8-mg... 

A new addition to this category is buprenorphine (Buprenex). This drug partially activates mu receptors but is an antagonist at kappa receptors. Because of these selective effects, buprenorphine has been advocated not only as an analgesic, but also as a treatment for opioid dependence and withdrawal.26 84 The use of this drug in treating opioid addiction is discussed in more detail later in this chapter. 

All opioids produce their effect by activating one or more of the three types of receptors. Thus analgesia involves the activation of the mu receptors that are located mainly at supraspinal sites and kappa receptors in the spinal cord delta receptors may also be involved but their relative contribution is unclear. Nevertheless, the actions of the opioids on these receptors is complex, as there is evidence that the same substance may act as a full agonist, or as an antagonist at different sites within the brain. 

In contrast to the mouse vas deferens, the guinea pig ileum contains predominately mu receptors and less kappa receptors, but no delta receptors. The function of mu and kappa receptors can be examined independently in the presence of a selective kappa antagonist (i.e., nor-BNI) and a mu antagonist (i.e., CTOP), respectively, similar to that described above for the mouse vas deferens [9]. The potency of mu and kappa agonists often exhibits higher potency in the guinea pig ileum than that obtained from the mouse vas deferens. 

Further studies in mouse vas deferens indicated that DPI-3290 is also active at mu opioid receptors. The intrinsic activity of DPI-3290 at mu opioid receptors was determined in the presence of the highly selective delta opioid receptor antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH) (3 pM) and the selective kappa opioid receptor antagonist nor-BNI (15 nM). Under these conditions, DPI-3290 again caused concentration-dependent inhibition of muscle contraction with a corresponding IC50 value of 6.2 2.0 nM. Although far less potent at kappa opioid receptors in comparison to its intrinsic activity at mu... 

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