Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man

Abstract

Background: In animals, activation of 5-HT(1) like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones.

Aims: To investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT(1) receptors, on fasting fundus tone and sensitivity to gastric distension in man.

Methods: A gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan.

Results: Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased.

Conclusions: Administration of the 5-HT(1) receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.

Figure 1

Representative tracing of intragastric volume, measured by a barostat, before and after administration of sumatriptan 6 mg subcutaneously at time 0.

Figure 2

Mean intragastric volume (n=11) at five minute intervals as measured with the barostat, before and after administration of sumatriptan 6 mg subcutaneously at time 0.

Figure 3

Pressure-volume relation obtained by gradually increasing isobaric gastric distensions before and after sumatriptan 6 mg subcutaneously (n=13). Linear model fitting revealed that sumatriptan causes a shift of the pressure-volume curve to significantly higher volumes (p<0.05). MDP, minimal distending pressure.

Figure 4

(A) Corresponding mean perception scores for gradually increasing isobaric distentions before and after sumatriptan 6 mg subcutaneously (n=13). (B) Corresponding mean perception scores for gradually increasing isovolumetric distensions before and after sumatriptan 6 mg subcutaneously (n=7). MDP, minimal distending pressure.

Figure 5

Number of subjects that reported first perception at a given distending volume before and after sumatriptan 6 mg subcutaneously, and number of subjects that reported discomfort at a given distending volume before and after sumatriptan 6 mg subcutaneously (n=7). Sumatriptan induced a significant shift of the volume-perception curve and of the volume-discomfort curve towards higher volumes (p<0.005; logistic regression).