Nifedipine's Synergistic Therapeutic Potential: Overcoming Challenges and Embracing Novel Applications in Pharmacotherapy

Nifedipine (NIFE) is a potent first-generation dihydropyridine calcium channel antagonist that belongs to the BCS-II drug. It inhibits calcium entry through L-type channels and disrupts the Ca-calmodulin complex, which ultimately blocks myosin light chain kinase activation, resulting in vasodilation, reduction in blood pressure, and negative chronotropic effect, thus slowing the heart rate. NIFE was used in the treatment of hypertension and angina. However, physicochemical properties, pharmacokinetic profile, mechanism of action, and therapeutic efficacy explain the widespread use of medication in various medical conditions. With a primary focus on its calcium channel-blocking properties, NIFE has demonstrated therapeutic efficacy in addressing classical vasospastic disorders, such as Raynaud's phenomenon, by modulating vascular function and reducing the episodes of digital ischemia. NIFE has been proven beneficial in ureteral stones by increasing their passage rates and in migraine by producing vasodilation. NIFE exhibits therapeutic effects by inhibiting proliferation and metastasis in colorectal cancer through reactivating tumour immunity. Similarly, it has great potential in obstetrics, as it effectively manages preterm labor by delaying the delivery and optimizing fetal conditions. Moreover, its applications can expand into evolving domains, such as achalasia, glaucoma, and chilblains, and potentially as an effective intervention against COVID-19.