Format

Send to

Choose Destination
Neuropharmacology. 1995 Mar;34(3):263-7.

5-Hydroxytryptamine3 receptor antagonism modulates a noxious visceral pseudoaffective reflex.

Author information

1
SmithKline Beecham Pharmaceuticals, Harlow, Essex, U.K.

Abstract

5-Hydroxytryptamine (5-HT) receptor agonists and antagonists were dosed intravenously (i.v.) and studied for their effects on the depressor cardiovascular pseudoaffective reflex evoked by acute noxious colo-rectal distension in the anaesthetized rat. Methiothepin (100 micrograms kg-1) caused an initial, unsustained blockade of evoked depressor responses whilst ketanserin (100 micrograms kg-1) was without effect. By comparison, ondansetron dose dependently inhibited evoked depressor responses and was maximally active at 100 micrograms kg-1, causing a 57.5 +/- 0.9% reduction. An ID50 value of 36.7 micrograms kg-1 was estimated by regression analysis. In contrast, granisetron caused complete blockade of the depressor response with an ID50 of 0.4 microgram kg-1. Bell-shaped dose-effect curves were demonstrated for both granisetron and ondansetron. Intrathecal dosing with granisetron (100 ng) into the thoracolumbar region of the spinal cord prevented the depressor response to colo-rectal distension, suggesting a spinal site of action. The pseudoaffective depressor responses were not facilitated by pre-dosing with the 5-HT receptor agonists, 8-OH DPAT, alpha-methyltryptamine or 1-phenyl-biguanide. However, 8-OH DPAT (100 micrograms kg-1) facilitated pressor responses. It is suggested that 5-HT3-like receptors may have a role in modulating depressor responses to visceral pain and that in this action different 5-HT3 receptor antagonists are not necessarily equi-effective.

PMID:
7630481
DOI:
10.1016/0028-3908(94)00159-p
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center