Prulac-2 (Prucalopride) Prucalopride is a dihydro benzofuran carboxamide derivative from the benzofuran family that selectively stimulates 5-HT4 receptors and thus, it presents enterokinetic properties. The high selectivity of prucalopride allowed further development as it prevented the cardiac adverse reactions observed due to the non-target effects of precedent therapies.
- This medication is used to treat chronic constipation
- Prokinetic Agent
- Selective serotonin 5HT4-receptor agonist
Mechanism of Action
Prucalopride acts as a selective stimulator of the 5-HT4 receptors while having no interaction with the hERG channel or 5-HT1 receptors, which lessens the cardiovascular risk found in other similar drugs. 5-HT4 receptors can be found throughout the gastrointestinal tract primarily in smooth muscle cells, enterochromaffin cells, and myenteric plexus. Its activation produces the release of acetylcholine which is the major excitatory neurotransmitter in the GI tract. Hence, prucalopride stimulates motility by interacting specifically with 5-HT4 receptors in the GI tract which causes a release of acetylcholine and further contraction of the muscle layer of the colon and relaxation of the circular muscle layer leading to the propulsion of luminal content.
In animal studies, prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon. As well as prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate.
Peak plasma time
Peak plasma concentration
AUC = 109 ng·hr/mL Steady-state achieved within 3-4 days
The bioavailability of prucalopride is >90%
Volume of DistributionVd
The steady-state volume of distribution of prucalopride is 623 L after intravenous administration.
Plasma Protein binding
The plasma protein binding of prucalopride is 30%.
Metabolized by liver enzyme CYP3A4. Prucalopride is not largely metabolized in the body and does not interact with the enzymes of the family of the cytochrome P450 enzymes nor the P glycoprotein. The metabolism of prucalopride only represents 6% of the administered dose and the remaining 94% is found as the unchanged drug.
The half-life of prucalopride is 1 day
Excretion – 84.2% of prucalopride is excreted through Urine while the remaining 13.3% is via feces.
Besides its needed effects, a drug may cause some undesired effects. Although not all of these adverse effects might appear, if they do occur they may require medical attention.
Consult with your doctor instantly if any of the following side effects occur:
- stomach pain