Antinociceptive

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. 

Anzini M, Canullo L, Braile C, et ah Synthesis, biological evaluation, and receptor docking simulations of 2-[(acylamino)ethyl]-1,4-benzodiazepines as kappa-opioid receptor agonists endowed with antinociceptive and antiamnesic activity. J Med Chem 46 3833-3864, 2003... 

French ED, Dillon K, Wu X Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 8 649—632, 1997 Fujinaga M, Maze M Neurobiology of nitrous oxide-induced antinociceptive effects. Mol Neurobiol 25 167-189, 2002... 

Schaddelee MP, Collins SD, DeJongh J, de Boer AG, Ijzerman AP, Danhof M. Pharmacokinetic/pharmacodynamic modelling of the anti-hyperalgesic and antinociceptive effect of adenosine A1 receptor partial agonists in neuropathic pain. Eur J Pharmacol 2005 May 9 514(2-3) 131-40. 

In further support of a pro-nociceptive role of CX3CL1 are data showing that the direct injection of CX3CL1 in the periaqueductal grey, a brain region mostly involved with analgesic responses, albeit un-effective by itself, results in inhibition of the antinociceptive effects induced by p, 5, and k opioid agonists (Chen et al. 2(X)7). 

Considerable evidence for opioid-chemokine interactions comes from studies of pain and inflammation, where the inherent relationships between pain, inflammation, and the counteracting antinociceptive influences of opioids have considerable biomedical implications. The adaptive changes in immune and nervous system function with chronic inflammation and pain further reveal the inherent interrelatedness between opioids (Ossipov et al. 2003 Evans 2004 Roy et al. 2006 Christie 2008)... 

Chen X, Geller EB, Rogers TJ, Adler MW (2007) The chemokine CX3CLl/fractaUdne interferes with the antinociceptive effect induced by opioid agonists in the periaqueductal grey of rats. Brain Res 1153 52-57... 

The furan derivative (23) has been tested in vivo in tests of motor activity (open-field test) and antinociception (hot-plate test) as well as its capacity to enhance the hypokinetic and/or analgesic actions of subeffective doses of... 

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

Noladin ether (3) was recently isolated from porcine brain [16] and found to bind to the CBi receptor (/fj = 21.2 nM), to bind weakly to the CB2 receptor K, > 3 /iM) and it causes typical cannabinoid-like effects such as sedation, hypothermia, intestinal immobility and mild antinociception in mice [16]. This endocannabinoid had previously been synthesised independently by both Mechoulam and co-workers [176] and Sugiura et al. [173]. SAR studies of this endocannabinoid are lacking in the literature, however, a recent publication highlighted the importance of the tetra-unsaturated C20 chain... 

Iwamoto, E.T. Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat Influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217 451-460, 1981. 

Itzhak, Y. Kalir, A. Weissman, B.A. and Cohen, S. Receptor binding and antinociceptive properties of phencyclidine opiatelike derivatives. jjj J. Pharmacol 72 305-311, 1981. 

Another significant cannabinoid activity that is mediated by the nervous system arises from the antinociceptive properties of these agents. Compelling evidence suggests that cannabimimetics are effective in the... 

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