Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT

Paalzow, Gudrun; Paalzow, Lennart

doi:10.1016/0014-2999(75)90048-5

Cited by 27 publications

(2 citation statements)

References 40 publications

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“…Much more recently Hotovy (1956) has reported that atropine sulphate at a very low dose (30,ugkg-') is able to induce analgesia in rabbits. On the other hand it is well known that atropine administered at a much higher dosage (0.5-5.Omgkg-') antagonizes antinociception induced by cholinomimetics such as physostigmine (Ireson, 1970) and oxotremorine (Paalzow & Paalzow, 1975;Bartolini et al, 1987). Bartolini et al (1980) reported that in rodents not only is atropine (1 mg kg-', s.c.) able to decrease the pain threshold but also clearly to potentiate naloxone hyperalgesia.…”

Section: Introduction Methodsmentioning

confidence: 99%

Investigation into atropine‐induced antinociception

Ghelardini

Malmberg-Aiello

Giotti

et al. 1990

British J Pharmacology

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1 The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot-plate, writhing and tail-flick tests. 2 Atropine dose-dependently produced analgesia, no effect and hyperalgesia. Analgesia was observed in both species with doses ranging from 1 to lOOug kg-while hyperalgesia was obtained with 5mg kg-3 Atropine antinociception was prevented by pirenzepine (0.1 ug per mouse, i.c.v.), dicyclomine (1Omg kg-1, i.p.), atropine-methylbromide (0.5 pg per mouse, i.c.v.) and hemicholinium-3 (1 pg per mouse, i.c.v.). Naloxone (1mgkg-1, i.p.), a-methyl-p-tyrosine (100mgkg-1, s.c.) and reserpine (2mgkg-1, i.p.) were ineffective. 4 The site of atropine analgesia is in the CNS since it exerts its antinociceptive effect also when injected i.c.v. (1-10 ng per mouse). Moreover drugs which do not cross the blood-brain barrier, such as hemicholinium-3, pirenzepine and atropine methylbromide, were unable to antagonize atropine analgesia if administered i.p. 5 Atropine also in vitro, showed a biphasic action on electrically-evoked guinea-pig ileum contractions. Concentrations between 10-14 and 10-12 M increased electrically and nicotine-evoked contractions but did not affect acetylcholine-and oxotremorine-evoked contractions. Concentrations above 10-9M inhibited both electrically-and drug (acetylcholine, nicotine and oxotremorine)-evoked contractions while they were ineffective on unstimulated ileum. 6 On the basis of the above findings, amplification of cholinergic transmission by very low doses of atropine is postulated, through a selective blockade of presynaptic muscarinic autoreceptors, as the likely mechanism of action. 7 Atropine antinociception, unlike oxotremorine antinociception, was obtained without any impairment of mouse rota-rod performance. 8 The antagonism by pirenzepine and dicyclomine of oxotremorine and atropine antinociception suggests that M1 muscarinic receptor subtypes are responsible for cholinergic analgesia.

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Section: Introduction Methodsmentioning

confidence: 99%

Investigation into atropine‐induced antinociception

Ghelardini

Malmberg-Aiello

Giotti

et al. 1990

British J Pharmacology

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“…This difference in finding may be due to the fact that a 5-hydroxytryptaminergic system may mediate pain mechanisms (Messing & Lytle 1977) and play a role in tremorine (Sethy et a1 1971) and presumably OTMN antinpciception in mice, whilst there is no evidence to implicate this system in cholinergic analgesia in the rat (Paalzow & Paalzow 1975;Koehn et a1 1978). It may also be possible that DFP-induced antinociception is indirectly mediated via an endogenous opioid system (Koehn et a1 1980) which is not shared by OTMN, despite the fact that the latter authors were unable to show cross tolerance between DFP and morphine, which may be expected if they share a common mechanism.…”

Section: Discussionmentioning

confidence: 90%

Stereospecific inhibition of oxotremorine-induced antinociception by (+)-isomers of opioid antagonists: comparison with opioid receptor agonists

Ben-Sreti¹,

Sewell²

1982

Journal of Pharmacy and Pharmacology

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The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5-enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg Kg-1 i.p.) or Mr-2266 (2.0 mg kg-1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.

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