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Although the putative 5-HT1P receptor has been implicated to have a role in peristalsis, experiments which suggest this function are preliminary or have measured only components of the reflex. We have, therefore, further characterized a reported agonist at this receptor (5-hydroxyindalpine; 5-OHIP) and investigated the effects of 5-OHIP and 5-hydroxytrytophan-dipeptide (5-HTP-DP), a reported 5-HT1P receptor antagonist, on distension-induced peristalsis in mouse colon. The effects of 5-OHIP on intracellular calcium, cyclic adenosine monophosphate concentrations or GTPγS binding were measured in cell lines expressing human recombinant 5-HT1A, 1B, 1D, 2A, 2B, 2C, 3, 4, 6, 7 and α1A, α1B, D1, D2, D3, H1, H3 receptors. The effects of 5-OHIP and 5-HTP-DP on peristalsis were assessed by measuring changes in frequency and times to reach threshold of peristaltic contractions, as well as the threshold and maximum pressures of each peristaltic stroke. 5-hydroxyindalpine (1 nmol L−1–10 μmol L−1) had no significant activity at any of the receptors studied. However, 5-OHIP (0.1 nmol L−1–1 μmol L−1) concentration-dependently increased the frequency of peristalsis (EC50 = 4.4 nmol L−1) and reduced the time taken to reach threshold and threshold pressure, without altering maximum pressures. The maximum effect of 5-OHIP was at 1 μmol L−1 (68.0 ± 14.5% increase in frequency); 10 μmol L−1 decreased peristalsis. 5-hydroxytrytophan-dipeptide (1–300 nmol L−1) also increased the frequency of peristalsis and prevented the actions of 5-OHIP. The higher concentration (1 μmol L−1) transiently inhibited peristalsis and after recovery, prevented the actions of 5-OHIP but not the excitatory activity of the cholinesterase inhibitor neostigmine. In summary, the present data demonstrate an interaction of ‘5-HT1P-ligands’ with the peristaltic reflex. However, the absence of an effect of 5-OHIP on a range of different monoamine receptors continues to highlight the need to investigate the identity of the putative 5-HT1P receptor. [ABSTRACT FROM AUTHOR]