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Non-clinical Cardiovascular Studies of Prucalopride.

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eMediNexus    30 December 2017

A new article published in The Journal of Pharmacology and Experimental Therapeutics reported on the nonclinical cardiovascular profile of the selective 5-HT4 receptor agonist prucalopride. This article elaborated on the results of in vitro and in vivo studies performed to assess the non-5-HT4 receptor-mediated effects of prucalopride on cardiovascular electrophysiological parameters. Additionally, human platelet aggregation and coronary artery contraction were studied, to exclude interactions that have been suggested to mediate the cardiovascular effects of tegaserod. Finally, cardiovascular endpoints were investigated in chronic, repeated dose toxicology studies at very high prucalopride doses. The results did not exhibit any relevant effects in any of the cardiovascular studies at concentrations at least 50 times the therapeutic plasma level. However, in one study, minor and transient increases in heart rate and blood pressure were noted upon first exposure to prucalopride. From the findings, it was concluded that prucalopride may provide therapeutic benefit without the cardiovascular risks reported for other 5-HT4 receptor agonists.6

References

  1. Conlon K, De Maeyer J, Bruce C et al. Nonclinical Cardiovascular Studies of Prucalopride, a Highly Selective 5-Hydroxytryptamine 4 Receptor Agonist. Journal of Pharmacology and Experimental Therapeutics. 2017:jpet.117.244079. doi:10.1124/jpet.117.244079.

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