Investigation into atropine‐induced antinociception

Ghelardini, Carla; Malmberg-Aiello, P.; Giotti, A; Malcangio, Marzia; Bartolini, Alessandro

doi:10.1111/j.1476-5381.1990.tb12087.x

Cited by 59 publications

(44 citation statements)

References 18 publications

(18 reference statements)

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“…This is in agreement with the reported action of thioperamide as a histamine H3 receptor antagonist, and the antinociception observed might well be due to blockade of the H3 receptor and, consequently, to increased endogenous histamine release. This mechanism of action is not surprising if one bears in mind that two postsynaptic antagonists of the opioid and cholinergic systems naloxone and atropine, have also been demonstrated to induce antinociception when administered at low doses which are ineffective on the postsynaptic site, but which are capable of blocking the respective presynaptic receptors (Levine et al, 1979;Ghelardini et al, 1990).…”

Section: Discussionmentioning

confidence: 97%

Role of histamine in rodent antinociception

Malmberg-Aiello

Lamberti

Ghelardini

et al. 1994

British J Pharmacology

109

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1 Effects of substances which are able to alter brain histamine levels on the nociceptive threshold were investigated in mice and rats by means of tests inducing three different kinds of noxious stimuli: mechanical (paw pressure), chemical (abdominal constriction) and thermal (hot plate). 2 A wide range of i.c.v. doses of histamine 2HCI was studied. Relatively high doses were dosedependently antinociceptive in all three tests: 5-100 ,g per rat in the paw pressure test, 5-50 g per mouse in the abdominal constriction test and 50-1I 00 g per mouse in the hot plate test. Conversely, very low doses were hyperalgesic: 0.5 ftg per rat in the paw pressure test and 0.1-1 g per mouse in the hot plate test. In the abdominal constriction test no hyperalgesic effect was observed. 3 The histamine H3 antagonist, thioperamide maleate, elicited a weak but statistically significant dose-dependent antinociceptive effect by both parenteral (10-40mgkg-') and i. 5 Thioperamide-induced antinociception was completely prevented by pretreatment with a nonhyperalgesic i.p. dose of (R)-a-methylhistamine in the mouse hot plate and abdominal constriction tests. Antagonism was also observed when both substances were administered i.c.v. in rats. 6 L-Histidine HCl dose-dependently induced a slowly occurring antinociception in all three tests. The doses of 250 and 500mgkg-', i.p. were effective in the rat paw pressure test, and those of 500 and 1500mgkg'1, i.p. in the mouse hot plate test. In the mouse abdominal constriction test 500 and 1000mgkg'1, i.p. showed their maximum effect 2h after treatment. 8 To ascertain the mechanism of action of the antinociceptive effect of L-histidine and metoprine, the two substances were also studied in combination with the histamine synthesis inhibitor (S)-a-fluoromethylhistidine and with (R)-o-methylhistamine, respectively. L-Histidine antinociception was completely antagonized in all three tests by pretreatment with (S)-a-fluoromethylhistidine HCl (50 mg kg', i.p.) administered 2 h before L-histidine treatment. Similarly, metoprine antinociception was prevented by (R)-a-methylhistamine dihydrogenomaleate 20 mg kg-', i.p. administered 15 min before metoprine. Both (S)-a-fluoromethylhistidine and (R)-a-methylhistamine were used at doses which did not modify the nociceptive threshold when given alone. 9 The catabolism product, 1-methylhistamine, administered i.c.v. had no effect in either rat paw pressure or mouse abdominal constriction tests.10 These results indicate that the antinociceptive action of histamine may take place on the postsynaptic site, and that its hyperalgesic effect occurs with low doses acting on the presynaptic receptor. This hypothesis is supported by the fact that the H3 antagonist, thioperamide is antinociceptive and the H3 agonist, (R)-a-methylhistamine is hyperalgesic, probably modulating endogenous histamine release. L-Histidine and metoprine, which are both able to increase brain histamine levels, are also able to induce antinociception in mice and rats. Involvement of the histaminer...

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Section: Discussionmentioning

confidence: 97%

Role of histamine in rodent antinociception

Malmberg-Aiello

Lamberti

Ghelardini

et al. 1994

British J Pharmacology

109

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“…While caffeine, like all drugs interacting with presynaptic muscarinic auto- (Ghelardini et al 1990) and heteroreceptors , produces antinociception without any visible side effects, the direct muscarinic agonists and cholinesterase inhibitors provoke, at the same time, antinociception and a clear cholinergic symptomatology (tremors, sialorrhoea, diarrhoea, lacrimation etc. ).…”

Section: Discussionmentioning

confidence: 99%

“…The doses and administration schedules of naloxone, CGP 35348, α-methyl-p-tyrosine and reserpine were suitable for preventing antinociception induced respectively by morphine (Ghelardini et al 1990), GABA B agonist baclofen (Malcangio et al 1991), amphetamine (Bartolini et al 1987) and the antidepressant drugs clomipramine and amitriptyline (Galeotti et al 1995).…”

Section: Discussionmentioning

confidence: 99%

“…It has long been known that ACh (Pedigo et al 1975), selective M 1 agonists such as McN-A-343 and AF-102B , unselective muscarinic agonists such as tremorine (Lenke 1958), oxotremorine (George et al 1962;Bartolini et al 1987), arecoline (Herz 1962), pilocarpine (Hendershot and Forsaith 1959) and cholinesterase inhibitors such as physostigmine (Harris et al 1969;Ireson 1970) and diisopropyl phosphorofluoridate (Lentz et al 1969) induce antinociception in laboratory animals by the activation of the cholinergic system. Moreover, the amplification of cholinergic neurotransmission induced by antagonism of muscarinic autoreceptors Gualtieri et al 1989;Ghelardini et al 1990) or, alternatively, by interaction with heteroreceptors ) located on presynaptic cholinergic terminals, produces a central antinociceptive effect.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Caffeine induces central cholinergic analgesia

Ghelardini¹,

Galeotti²,

Bartolini³

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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The antinociceptive effect of caffeine was examined by using the hot-plate, abdominal constriction tests in mice and the tail flick and paw-pressure tests in rats. Caffeine (1-5 mg kg -1 s.c. in mice; 2.5-5 mg kg -1 i.p. in rats) produced significant antinociception in both species which was prevented by atropine (5 mg kg -1 i.p.), pirenzepine (0.1 µg per mouse i.c.v.), hemicholinium-3 (1 µg/ mouse i.c.v.) and N 6 -cyclopentyladenosine (5 µg/mouse i.c.v.), but not by naloxone (1 mg kg -1 i.p.), CGP 35348 (100 mg kg -1 i.p.), α-methyl p-tyrosine (100 mg kg -1 i.p.) and reserpine (2 mg kg -1 i.p.). Intracerebroventricular injection of caffeine in mice at doses (2.5-5 µg per mouse) which were largely ineffective by parenteral routes, induces an antinociception whose intensity equalled that obtainable s.c. or i.p. In the antinociceptive dose-range, caffeine did not produce any behavioural impairment as revealed by the rotarod and Irwing tests. On the basis of the above data, it can be postulated that caffeine exerts an antinociceptive effect mediated by central amplification of cholinergic transmission.

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“…In other studies (Ghelardini et al, 1990, it has been reported that atropine in animal experiments is either a cholinomimetic or a cholinolytic drug, depending on the dose. Very low doses of atropine which were inadequate for blocking muscarinic receptors (1-100 µg/kg in vivo; 10 -14 -10 -12…”

Section: Modes Of Actionmentioning

confidence: 96%

Scientific Opinion on Tropane alkaloids in food and feed

2013

EFS2

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The European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the risks to human and animal health related to the presence of tropane alkaloids (TAs) in food and feed. TAs are secondary metabolites which occur in several plant families. Although more than 200 different TAs have been identified in various plants, respective data on toxicity and occurrence in food and feed are limited. Therefore, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) could only perform a risk assessment on (-)-hyoscyamine and (-)-scopolamine, the two TAs for which occurrence and toxicity data were available. Since the pharmacological effects of (-)-hyoscyamine and (-)-scopolamine occur within a short time after administration, the CONTAM Panel concluded that it was appropriate to establish an Acute Reference Dose (ARfD) for these substances. Based on the results for decreased heart rate in a human volunteer study, the CONTAM Panel established a group ARfD of 0.016 µg/kg body weight (b.w.) expressed as the sum of (-)-hyoscyamine and (-)-scopolamine, assuming equivalent potency. Results on TAs in 124 food and 611 feed samples were collected in two Member States. Most of the food and feed samples were left-censored (below limit of detection/limit of quantification). A reliable exposure estimate was only possible for one food and one age class (toddlers). Based on the limited information, the CONTAM Panel concluded that the dietary exposure of toddlers could be up to seven times the group ARfD and could exceed the group ARfD on approximately 11 to 18 % of consumption days. TA toxicosis in livestock and companion animals is relatively rare. © European SUMMARYFollowing a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on the risks to human and animal health related to the presence of tropane alkaloids (TA) in food and feed.TAs are secondary metabolites which naturally occur in plants of several families including Brassicaceae, Solanaceae (e.g. mandrake, henbane, deadly nightshade, Jimson weed) and Erythroxylaceae (including coca). The TAs are found in all parts of the plants and are responsible for the toxic effects of some of these plants. TAs contain an azabicyclo[3.2.1]octane ring structure. The common structural element is the tropane skeleton, (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octane. The group of TAs comprises more than 200 compounds and the wide range of compounds occurring especially in the Solanaceae family arises from the esterification of tropine with a variety of acids, such as acetic acid, propanoic acid, isobutyric acid, isovaleric acid, 2-methylbutyric acid, tiglic acid, (+)-α-hydroxy-β-phenylpropionic acid, tropic acid, and atropic acid.Although more than 200 different TAs were so far identified in various plants, respective data on their occurrence in food and feed and on toxicity are limited. The most studied TAs are (-)-hyoscyamine and (-)-scopolamine, which in contrast to the (+...

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Investigation into atropine‐induced antinociception

Cited by 59 publications

References 18 publications

Role of histamine in rodent antinociception

Role of histamine in rodent antinociception

Caffeine induces central cholinergic analgesia

Scientific Opinion on Tropane alkaloids in food and feed

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