Antinociception, receptors

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... 

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. 

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. 

Kamei J, Saitoh A, Ohsawa M, Suzuki T, Misawa M, Nagase H, Kasuya Y. Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice. Eur J Pharmacol 1995 276 131-135. 

Jiirgensen S, Dalbo S, Angers P, Santos AR, Ribeiro-do-Valle RM. Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa. Pharmacol Biochem Behav 2005 81 466-477. 

Berrendero, R., Kieffer, B., Maldonado, R. Attenuation of nicotine-induced antinociception, rewarding effects and dependence in mu-opioid receptor knock out mice. J. Neurosci. 22 10935, 2002. 

Histamine also induces antinociceptive (i.e. pain-relieving) responses in animals after microinjection into several brain regions [73, 74]. H, and H2 mechanisms are significant and both neuronal and humoral mechanisms may be involved. Brain H2 receptors appear to mediate some forms of endogenous analgesic responses, especially those elicited by exposure to stressors [75]. Many of the modulatory actions of histamine discussed above appear to be activated as part of stress responses. For reasons that remain unclear, histamine releasers, such as thioperamide, show only mild, biphasic antinociceptive actions, even though histamine is a potent and effective analgesic substance. Outside the brain, both H and H3 receptors exist on certain types of sensory nerves and activation of these receptors promotes and inhibits, respectively, peripheral nerve transmission related to pain and/or inflammation [76,77]. 

Lamberti, C., Bartolini, A., Ghelardini, C. and Malmberg-Aiello, P. Investigation into the role of histamine receptors in rodent antinociception. Pharmacol. Biochem. Behav. 53 567-574,1996. 

Rouleau, A., Stark, H., Schunack, W. and Schwartz, J. C. Anti-inflammatory and antinociceptive properties of BP 2-94, a histamine H-3-receptor agonist prodrug./. Pharmacol. Exp. Ther. 295 219-225, 2000. 

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