Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved.
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PMID:Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT. 23 55

Recent studies suggested that the L-arginine/nitric oxide (NO)/cyclic GMP pathway is involved in the modulation of pain perception. The present experiments were undertaken to find out the role of this pathway in the antinociception induced by oxotremorine administration. Male mice of the CD-1 strain were injected with different doses of the muscarinic agonist oxotremorine (0.005, 0.01, 0.02, 0.03 mg/kg i.p.) 5 min after the administration of saline solution or the inhibitors of NO synthase NG-nitro-L-arginine methyl ester (L-NAME: 10 and 20 mg/kg, i.p.) or NG-nitro-L-arginine (N-ARG: 10 and 20 mg/kg i.p.). Oxotremorine induced a dose- and time-dependent analgesic effect in mice, which was significantly increased by L-NAME and N-ARG administration. Either doses of the NO inhibitors given alone had no effect on the nociceptive threshold. The present results show a role of NO in the antinociception mediated by the muscarinic receptor stimulation and suggest that it exerts an inhibitory action on cholinergic analgesia.
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PMID:Nitric oxide synthase inhibitors enhance the antinociceptive effects of oxotremorine in mice. 943 49

The central and peripheral effects of a series of Oxotremorine/Oxotremorine-M derivatives, previously characterized as muscarinic agonists in isolated preparations, were investigated in in vivo experiments. The molecules were tested for their antinociceptive activity (formalin licking and acetic acid writhing tests) and for their ability to induce tremor in mice. Peripheral cholinergic effects such as salivation, bradycardia, hypotension and intestinal hypermotility were studied in anaesthetized rats. All of the acetylenic compounds acted as muscarinic analgesics displaying the same order of potency shown in in vitro studies. The Oxotremorine-like subset showed a clearer distinction between doses producing antinociception and doses exerting undesirable central/peripheral side effects compared to the Oxotremorine-M derivatives. The most promising profile was displayed by the isoxazolin-3-one Oxotremorine-like derivative (compound 1a), which was characterized by a wider therapeutic window than that of the parent molecule Oxotremorine. Indeed, it produced atropine-sensitive analgesia (ID50 about 0.1 mg/kg i.p.) in the absence of tremorogenic (EC50 2.73 mg/kg i.p.) and cardiovascular effects while lethality occurred only at higher doses (LD50 19 mg/kg i.p.). These results suggest that such a derivative could be a candidate for further development of selective muscarinic analgesics.
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PMID:Evidence for specific analgesic activity of a muscarinic agonist selected among a new series of acetylenic derivatives. 1127 Jun 24