Rectal antinociceptive properties of alverine citrate are linked to antagonism at the 5-HT1A receptor subtype.

Abstract

Serotonin (5-HT) is considered as a major mediator causing hyperalgesia and is involved in inflammatory reactions and irritable bowel syndrome. Alverine citrate may possess visceral antinociceptive properties in a rat model of rectal distension-induced abdominal contractions. This study was designed to evaluate the pharmacological properties of alverine citrate in a rat model of rectal hyperalgesia induced by 5-HTP (5-HT precursor) and by a selective 5-HT1A agonist (8-OH-DPAT) and to compare this activity with a reference 5-HT1A antagonist (WAY 100635). At 4 h after their administration, 5-HTP and 8-OH-DPAT increased the number of abdominal contractions in response to rectal distension at the lowest volume of distension (0.4 mL). When injected intraperitoneally before 8-OH-DPAT and 5-HTP, WAY 100635 (1 mg kg(-1)) blocked their nociceptive effect, but also reduced the response to the highest volume of distension (1.6 mL). Similarly, when injected intraperitoneally, alverine citrate (20 mg kg(-1)) suppressed the effect of 5-HTP, but not that of 8-OH-DPAT. However, when injected intracerebroventricularly (75 microg/rat) alverine citrate reduced 8-OH-DPAT-induced enhancement of rectal distension-induced abdominal contractions. In-vitro binding studies revealed that alverine citrate had a high affinity for 5-HT1A receptors and a weak affinity for 5-HT3 and 5-HT4 subtypes. These results suggest that 5-HTP-induced rectal hypersensitivity involves 5-TH1A receptors and that alverine citrate acts as a selective antagonist at the 5-HT1A receptor subtype to block both 5-HTP and 8-OH-DPAT-induced rectal hypersensitivity.

• Authors: A M Coelho, L Jacob, J Fioramonti, L Bueno
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 53 Issue 10 Pg. 1419-26 (Oct 2001) ISSN: 0022-3573 [Print] England
• PMID: 11697552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Piperazines
• Propylamines
• Pyridines
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists
• alverine
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• 5-Hydroxytryptophan

Topics

• 5-Hydroxytryptophan (antagonists & inhibitors, pharmacology)
• Analgesics, Non-Narcotic (administration & dosage, pharmacology)
• Animals
• Catheterization
• Cell Membrane (drug effects, metabolism)
• Cells, Cultured
• Electromyography
• Hyperalgesia (drug therapy)
• Injections, Intraventricular
• Male
• Pain (drug therapy)
• Piperazines (antagonists & inhibitors, pharmacology)
• Propylamines (administration & dosage, agonists, pharmacology)
• Pyridines (antagonists & inhibitors, pharmacology)
• Rats
• Rats, Wistar
• Receptors, Serotonin (drug effects)
• Receptors, Serotonin, 5-HT1
• Rectum
• Serotonin Antagonists (administration & dosage, pharmacology)