Tegaserod was metabolized in human liver microsomes to O-desmethyl tegaserod at a low rate. Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pK i =7.5, 8.4 and 7.0, respectively). Tegaserod (0.1-3 μM) inhibits 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA 2 =8.3), consistent with 5-HT2B receptor antagonist activity.
Tegaserod increases the amplitude of excitatory postsynaptic currents mediated by nicotinic acetylcholine receptors which may contribute to the prokinetic effects by facilitating excitatory neurotransmission in mice. Tegaserod (0.1 mg/kg) significantly accelerates the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. Tegaserod (5, 10, 50, 100 μg/mL) promotes hindlimb motor function at 6 weeks after spinal cord injury compared to the control group receiving vehicle only.