Comparison of potencies of 5-HT3 receptor antagonists at inhibiting aversive behavior to illumination and the von Bezold-Jarisch reflex in the mouse

Eglen, Richard M.; Lee, C.-H.; Khabbaz, Maram; Fontana, David; Daniels, Scott E.; Kilfoil, T.; Wong, Erik H. F.

doi:10.1016/0028-3908(94)90013-2

Cited by 16 publications

(7 citation statements)

References 37 publications

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“…The presence of opposing behaviourally inhibitory and disinhibitory 5-HT mechanisms may contribute to an understanding of the controversial data on the varying eects of pharmacological manipulations of 5-HT function. For example, Eglen et al (1994) showed that S(7)-zacopride in the C57BL/6 mouse strain had an anxiolytic pro®le in the mouse light/dark test, whereas in the present study with BKW mice it was ineective. However, in the presence of ritanserin, the present study demonstrated disinhibitory potencies for both R(+)-and S(7)-zacopride similar to those found by Eglen et al (1994).…”

Section: Discussioncontrasting

confidence: 71%

“…For example, Eglen et al (1994) showed that S(7)-zacopride in the C57BL/6 mouse strain had an anxiolytic pro®le in the mouse light/dark test, whereas in the present study with BKW mice it was ineective. However, in the presence of ritanserin, the present study demonstrated disinhibitory potencies for both R(+)-and S(7)-zacopride similar to those found by Eglen et al (1994). Such data may indicate that the C57BL/6 mouse strain either lacks the ritanserin sensitive mechanism or that it operates at a reduced level to that found in the BKW mouse.…”

Section: Discussioncontrasting

confidence: 71%

“…From these experiments a tentative identification of the 5‐HT receptor mediating the disinhibitory effects of the ritanserin/5‐hydroxytryptophan interaction and diazepam was made by use of the mixed 5‐HT 3 /5‐HT 4 receptor antagonists tropisetron and SDZ205–557 (Eglen et al , 1994). The latter agents, but not the selective 5‐HT 3 receptor antagonist ondansetron, were found to antagonize the disinhibitory effects of the ritanserin/5‐hydroxytryptophan interaction and diazepam treatments (Costall et al , 1993b; Cheng et al , 1994): the 5‐HT 4 receptor was hypothesized to mediate the disinhibitory effects.…”

Section: Introductionmentioning

confidence: 99%

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The influence of 5‐HT₂and 5‐HT₄receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

Costall¹,

Naylor²

1997

British J Pharmacology

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1 The ability of 5-HT 2 and 5-HT 4 receptor antagonists to modify the disinhibitory pro®le of diazepam and other agents was investigated in male BKW mice in the light/dark test box. 2 The 5-HT 2A/2B/2C receptor antagonists ritanserin, MDL11939 and RP62203 and also methysergide, which failed to modify mouse behaviour when administered alone, caused dose-related enhancements (4 to 8 fold) in the potency of diazepam to disinhibit behavioural responding to the aversive situation of the test box. 3 Ritanserin was shown to enhance the disinhibitory potency of other benzodiazepines, chlordiazepoxide (4 fold), temazepam (10 fold) and lorazepam (10 fold), the 5-HT 1A receptor ligands, 8-OH-DPAT (25 fold), buspirone (100 fold) and lesopitron (500 fold), the 5-HT 3 receptor antagonists, ondansetron (100 fold) R(+)-zacopride (100 fold) and S(7)-zacopride (greater than a 1000 fold), the substituted benzamides, sulpiride (10 fold) and tiapride (5 to 10 fold) and the cholecystokinin (CCK) A receptor antagonist, devazepide (100 fold). It also reduced the onset of action of disinhibition following treatment with the 5-HT synthesis inhibitor parachlorophenylalanine. Ritanserin failed to enhance the disinhibitory eects of the CCK B receptor antagonist CI-988, the angiotensin AT 1 receptor antagonist losarten or the angiotensin converting enzyme inhibitor ceranapril. 4 The 5-HT 4 receptor antagonists SDZ205-557, GR113808 and SB204070 caused dose-related reductions in the disinhibitory eect of diazepam, returning values to those shown in vehicle treated controls. The antagonists failed to modify mouse behaviour when administered alone. 5 GR113808 was also shown to cause a dose-related antagonism of the disinhibitory eects of chlordiazepoxide, lorazepam, 8-OH-DPAT, buspirone, lesopitron, ondansetron, R(+)-zacopride, sulpiride, tiapride, devazepide, CI-988, losarten, ceranapril and parachlorophenylalanine. 6 It was concluded that in BKW mice (a) the failure of 5-HT 2 and 5-HT 4 receptor antagonists when administered alone to modify behaviour in the light/dark test indicates an absence of an endogenous 5-HT tone at the 5-HT 2 and 5-HT 4 receptors and (b) the enhancement by the 5-HT 2 receptor antagonists and attenuation by the 5-HT 4 receptor antagonists of drug-induced disinhibition indicates a plurality of 5-HT receptor involvement in the mediation of drug-induced disinhibitory pro®les in the mouse.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussioncontrasting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The influence of 5‐HT₂and 5‐HT₄receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

Costall¹,

Naylor²

1997

British J Pharmacology

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“…Serotonin (5-HT) may be a key chemical in blood pressure regulation and vasovagal syncope. 59 Blood pressure and heart rate can be modified by stimulating both peripheral and central serotonin receptors, and different effects on these values may occur depending on the subtype of serotonin receptor stimulated (5-HT 1 , 5-HT 2 , 5-HT 3 ). Peripheral 5-HT 3 receptors are highly associated with the bradycardia and hypotension in animal models of vasovagal syncope.…”

Section: -Ht 3 Receptorsmentioning

confidence: 99%

“…13 Selective blockade of 5-HT 3 receptors fully prevented components of vasovagal syncope in animal models with exogenous administration of serotonin. 59,67 A pilot study compared the effects of exogenous serotonin challenge with pretreatment of either 20-or 50-µg/kg doses of the 5-HT 3 receptor antagonist granisetron. A dose-response relationship for blood pressure maintenance was seen.…”

Section: -Ht 3 Receptorsmentioning

confidence: 99%

A Review of Pathophysiology and Therapy of Patients with Vasovagal Syncope

White

Tsikouris

2000

Pharmacotherapy

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Vasovagal syncope is a common disorder that can compromise quality of life and lead to significant morbidity. It is characterized by an initial exaggerated sympathetic output followed by parasympathetic activation and sympathetic withdrawal, as shown by diagnostic head-up tilt (HUT) table testing. Numerous drugs have been evaluated for treating this disorder. beta-Blockers are well studied and commonly administered but are specifically more efficacious in patients with isoproterenol HUT than in those with regular HUT. The role of the serotonergic system has captured new interest. Selective serotonin reuptake inhibitors show promising results in preventing vasovagal syncope in treatment-refractory patients. Also, new investigations suggest that serotonin receptor antagonism may be beneficial. Despite these findings, definitive treatment does not exist.

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Efficacy of Intravenous Granisetron in Suppressing the Bradycardia and Hypotension Associated with a Rabbit Model of the Bezold‐Jarisch Reflex

White

Chow

Fan

et al. 1998

The Journal of Clinical Pharma

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This study investigated whether granisetron, a 5-HT3 receptor antagonist, can alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold-Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the carotid arteries one day before experimental hemorrhage. On the day of the study, the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal volume of saline. Five minutes after administration of granisetron or saline, hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood pressure (BP) and heart rates were obtained at frequent intervals until systolic BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before achieving the target systolic BP of 80 mmHg. The group receiving granisetron demonstrated the same ability to increase their heart rate from baseline as the saline group. However, the granisetron group had a final heart rate that was closer to their maximal heart rate than the saline group. In this animal model, granisetron was significantly more effective at preventing inappropriate heart rate slowing and allowed significantly more blood to be removed before reaching the target blood pressure. This implies that granisetron may be effective in preventing vasovagal syncope, although further study should be carried out to verify these potentially interesting findings.

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Comparison of potencies of 5-HT3 receptor antagonists at inhibiting aversive behavior to illumination and the von Bezold-Jarisch reflex in the mouse

Cited by 16 publications

References 37 publications

The influence of 5‐HT₂and 5‐HT₄receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

The influence of 5‐HT₂and 5‐HT₄receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

A Review of Pathophysiology and Therapy of Patients with Vasovagal Syncope

Efficacy of Intravenous Granisetron in Suppressing the Bradycardia and Hypotension Associated with a Rabbit Model of the Bezold‐Jarisch Reflex

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Comparison of potencies of 5-HT3 receptor antagonists at inhibiting aversive behavior to illumination and the von Bezold-Jarisch reflex in the mouse

Cited by 16 publications

References 37 publications

The influence of 5‐HT2and 5‐HT4receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

The influence of 5‐HT2and 5‐HT4receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

A Review of Pathophysiology and Therapy of Patients with Vasovagal Syncope

Efficacy of Intravenous Granisetron in Suppressing the Bradycardia and Hypotension Associated with a Rabbit Model of the Bezold‐Jarisch Reflex

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Product

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The influence of 5‐HT₂and 5‐HT₄receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

The influence of 5‐HT₂and 5‐HT₄receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test