Mu opioid agonists

Codd EE. (1995). High affinity ibogaine binding to a mu opioid agonist site. Life Sci. 57(20) PL315-... 

Yoshida M, Yokoo H, Tanaka T, Mizoguchi K, Emoto H, et al. 1993. Facilitatory modulation of mesolimbic dopamine neuronal activity by a mu-opioid agonist and nicotine as examined with in vivo microdialysis. Brain Res 624(1-2) 277-280. 

Yates SL, Bencherif M, Fluhler EN, LippieUo PM (1995) Up-regulation of nicotinic acetylcholine receptors following chronic exposure of rats to mainstream cigarette smoke or alpha 4 beta 2 receptors to nicotine, Biochem Pharmacol 50 2001-2008 Yeomans J, Baptista M (1997) Both nicotinic and muscarinic receptors in ventral tegmental area contribute to brain-stimulation, Pharmacol Biochem Behav 57 915-921 Yoshida M, Yokoo H, Tanaka T, Mizoguchi K, Emoto H, Ishii H, Tanaka M (1993) Facilitatory modulation of mesolimbic dopamine neuronal-activity by a mu-opioid agonist and nicotine as examined with in-vivo microdialysis. Brain Res 624 277-280... 

Dogrul, A., Yesilyurt, O., Isimer, A., Guzeldemir, M.E. L-type and T-type calcium channel blockade potentiate the analgesic effects of morphine and selective mu opioid agonist, but not to selective delta and kappa agonist at the level of the spinal cord in mice, Pain 2001, 93, 61-68. 

Eisenberg, E., McNicol, E. D., and Carr, D. B. (2006). Efficacy of mu-opioid agonists in the treatment of evoked neuropathic pain Systematic review of randomized controlled trials. Eur. J. Pain 10, 667-676. 

Patent applications have been filed covering compounds without the distal nitrogen constrained in a ring directly attached to the benzhydryl carbon. SmithKline Beecham scientists filed a patent application on diaryldi-amines typified by compound 48 [33], and Meiji Seika Kaisha researchers filed a patent application covering diphenylalkylpiperidines as mu opioid agonists—for instance, compound 49 [34]. 

The identification of several compounds that have in vitro potencies in the 1-5 nM range at both the mu and delta receptors, such as compounds 54 and 55 (Fig. 11), has provided useful tools to test the pharmacological effects of mixed delta/mu opioid agonists in human clinical trials. 

Bubacz DG, Davis AO, Dickerson SFI, Flarris PA, McNutt RW, Collins MA, Chang K-J. Synthesis of novel mixed delta-mu opioid agonists. Book of Abstracts, 213th ACS National Meeting, San Francisco 1997 MEDI-050. 

Biochemical studies have shown in vitro and in vivo differential inhib-itory/stimulatory modulation of spinal and supraspinal CCK release by mu and delta opioid agonists. Thus, delta opioid agonists enhance the release of CCK, whereas stimulation of mu opioid receptors reduces its release [81,82], Moreover, it has been shown that activation of CCKi receptors potentiates the analgesic responses induced by mu opioid agonists or by endogenous enkephalins, protected from their catabolism by the dual inhibitor RB 101, while activation of CCK2 receptors reduces them [80]. 

In the dog, electrically evoked contractions of the lower esophageal sphincter are inhibited by DPDPE, a response interpreted to indicate the involvement of delta opioid receptors [72]. On the other hand, DADLE increases lower esophageal sphincter pressure in the opossum. As the mu opioid agonists meperidine and buprenorphine both reduce sphincter pressure, the opposite effect of DADLE is probably mediated by delta opioid receptors [73],... 

The antinociceptive effects of mu opioid agonists within the RVM require activation of a class of neurons termed off-cells that exert a net inhibitory effect on nociception [4-6], Mu opioid activation of off-cells is indirect, and triggered by disinhibition. In addition to the indirect activation of off-cells, mu opioids inhibit another class of neurons in RVM, termed on-cells. This inhibition is direct, but suppression of on-cell discharge is not sufficient to produce behavioral analgesia. Opioid inhibition of on-cells may however assume an important role in inflammatory pain states, in which these neurons likely contribute to hyperalgesia [7]. 

Studies in animals and primates with these highly selective delta agonists begin to reveal that unlike mu opioid agonists such as morphine, oxy-contin, fentanyl, etc., agents acting at the delta receptor are unlikely to produce addictive liability and respiratory depression. In fact, delta agonists may actually counteract those side effects induced by mu opioids. 

Mucha RF, Herz A (1985) Motivational properties of kappa and mu-opioid agonists studied with place and taste preference conditioning procedures. Psychopharmacol 82 241-245... 

Khasar SG, Wang J-F, Taiwo YO, Heller PH, Green PG, Levine JD (1995) Mu-opioid agonist enhancement of prostaglandin-induced hyperalgesia in the rat a G-protein beta gamma subunit-mediated effect Neuroscience 67 189-195... 

Zemig G, Issaevitch T, Broadbear JH, Burke TF, Lewis JW, Brine GA, Woods JH (1995) Receptor reserve and affinity of mu-opioid agonists in mouse antinociception - correlation with receptor-binding. Life Sci 57 2113-2125... 

Qcero TJ, Ellis MS, Paradis A, Ortbal Z. Determinants of fentanyl and other potent mu opioid agonist misuse in opioid-dependent individuals. Pharmacoepide-miol Drug Saf 2010 19(10) 1057-63. 

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