Blockade of motion‐ and cisplatin‐induced emesis by a 5‐HT<sub>2</sub> receptor agonist in <i>Suncus murinus</i>

Okada, Fumihiko; Saito, Hiroshi; Matsuki, Norio

doi:10.1111/j.1476-5381.1995.tb13293.x

Cited by 33 publications

(11 citation statements)

References 21 publications

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“…Indeed, Suncus murinus positively responds to various emetic stimuli including motion, X-radiation, and emetogenic substances such as nicotine, copper salt, and cisplatin (18,19). In our experiments, oral administration of a SSRI (paroxetine, fluboxamine, or sertraline) increased the incidence of vomiting in animals, shortened the latency to the first emetic episode, and increased total emetic episodes.…”

Section: Discussionmentioning

confidence: 65%

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

2013

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Abstract. Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, they frequently cause gastrointestinal adverse effects, such as nausea and emesis. In the present study, we investigated the anti-emetic effect of mosapride, a 5-HT 4 receptor agonist, on SSRIs-induced emesis in Suncus murinus and dogs. We also examined the effect of mosapride on SSRIs-induced delay in gastric emptying and increase in gastric vagal afferent activity in rats. Oral administration of paroxetine, but not its subcutaneous administration, dose-dependently caused emesis in both animals. Mosapride inhibited paroxetine-induced emesis in Suncus murinus and dogs with ID 50 values of 7.9 and 1.1 mg/kg, respectively. The anti-emetic effect of mosapride was partially inhibited by SB207266, a selective 5-HT 4 antagonist. Intragastric administration of paroxetine increased gastric vagal afferent discharge in anesthetized rats. Mosapride failed to suppress this increase. On the other hands, mosapride improved the delay in gastric emptying caused by paroxetine in rats. We have shown in this study that oral administration of SSRIs causes emesis and activates gastric vagal afferent activity in experimental animals and that mosapride inhibits SSRIs-induced emesis, probably via improvement of SSRIs-induced delay in gastric emptying. These findings highlight the promising potential of mosapride as an anti-emetic agent.

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Section: Discussionmentioning

confidence: 65%

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

2013

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“…5-MeODMT (Weil and Davis, 1994), 5-MeOAMT (Kantor et al, 1980), and R-DOI (Glennon et al, 1982) have been shown to enter the central nervous system following systemic dosing, suggesting that a centrally mediated mechanism may be responsible for the reduction in IOP observed with 5-HT 2 agonists. However, the nonselective peripheral 5-HT 2 agonists 5-HOAMT (Baudrie and Chaouloff, 1992;Okada et al, 1995) and 5-HODMT (McBride, 2000) also decreased IOP in the monkey following topical administration. Furthermore, the topical application of R-DOI to the normal (nonlasered normotensive) eye of the monkeys resulted in a significant reduction of IOP in this treated normal left eye; however, no reduction of IOP was observed in the untreated (undosed) hypertensive contralateral eye (Table 7).…”

mentioning

confidence: 99%

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

May¹,

McLaughlin²,

Sharif³

et al. 2003

J Pharmacol Exp Ther

106

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Published investigations of serotonin-1A (5-hydroxytryptamine 1A ; 5-HT 1A ) receptor agonists and serotonin-2A (5-hydroxytryptamine 2A ; 5-HT 2A ) receptor antagonists in nonprimate species provide conflicting results with regard to their intraocular pressurelowering efficacy. Thus, their therapeutic utility in the treatment of human glaucoma has been confusing. We evaluated the effect of selected 5-HT 1A agonists and 5-HT 2A receptor antagonists on intraocular pressure in a nonhuman primate model, the conscious cynomolgus monkey with laser-induced ocular hypertension. Neither selective 5-HT 1A agonists [e.g., R-8-hydroxy-2-(di-n-propylamino)tetralin and flesinoxan] nor selective 5-HT 2 receptor antagonists [e.g.,pressure in the primate model following topical ocular administration. However, compounds that function as agonists at both the 5-HT 1A and 5-HT 2 receptors were found to effectively lower intraocular pressure in the model: 5-hydroxy-␣-methyltryptamine, 5-methoxy-␣-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine (bufotenine), and 5-methoxy-N,N-dimethyltryptamine. Furthermore, the selective 5-HT 2 receptor agonist R-(Ϫ)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane lowered intraocular pressure in the primate model, demonstrating a pharmacological response associated with activation of the 5-HT 2 receptor. These observations suggest that compounds that function as efficient agonists at 5-HT 2 receptors should be considered as potential agents for the control of intraocular pressure in the treatment of ocular hypertension and glaucoma in humans.Identification of several of the numerous serotonin receptors in ocular tissues of the anterior segment of the eye, including the iris-ciliary body of rabbit (Chidlow et al., 1998) and human (Martin et al., 1992), suggests that this neurotransmitter may play an important role in the regulation of intraocular pressure (IOP). Serotonin (5-hydroxytryptamine; 5-HT) is also found in the aqueous humor of humans (Veglio et al., 1998) and other mammals (Boerrigter et al., 1992). These observations have generated considerable interest in the role that serotonin might have in aqueous humor dynamics and even whether 5-HT might be involved in the development of ocular hypertension and glaucoma. There have been numerous conflicting reports on the effect of 5-HT and various 5-HT receptor ligands on IOP in the rabbit, dog, and humans. These observed differences in IOP response may be due to species differences, route of administration, or the lack of 5-HT receptor selectivity of the agents evaluated. For example, 5-HT has been shown to lower IOP in rabbits following intravenous injection (Chiang, 1974). However, when injected intracamerally in the rabbit, a rise in IOP was observed (Krootila et al., 1987). Furthermore, topical ocular administration of 5-HT to the rabbit was reported to result in either a decrease (Krootila et al., 1987) or an increase (Meyer-Bothling et al., 1993) in IOP.Article, publication date, and citation information can be found at

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“…8-OH-DPAT, buspirone (currently used in psychiatry), flesinoxan and lesopitron, which, in animals, can reduce motion-, copper sulphate-and cisplatin-induced emesis [18,24,30,32]. Activation of somatodendritic 5-HT 1A autoinhibitory receptors in the raphé nuclei reduces 5-HT cell firing and 5-HT release throughout the central serotonergic system.…”

Section: Continuing Involvement Of 5ht Receptorsmentioning

confidence: 99%

Neuropharmacology of emesis and its relevance to anti-emetic therapy

Andrews

Naylor

Joss

1998

Supportive Care in Cancer

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Blockade of motion‐ and cisplatin‐induced emesis by a 5‐HT₂ receptor agonist in Suncus murinus

Cited by 33 publications

References 21 publications

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Neuropharmacology of emesis and its relevance to anti-emetic therapy

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Blockade of motion‐ and cisplatin‐induced emesis by a 5‐HT2 receptor agonist in Suncus murinus

Cited by 33 publications

References 21 publications

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT1A and 5-HT2 Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Neuropharmacology of emesis and its relevance to anti-emetic therapy

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Blockade of motion‐ and cisplatin‐induced emesis by a 5‐HT₂ receptor agonist in Suncus murinus

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys