Synthesis of Novel 4-[1-(4-fluorobenzyl)-5-imidazolyl] Dihydropyridines and Studying their Effects on Rat Blood Pressure

OBJECTIVES Calcium-channel blockers have an important role in the treatment of several cardiovascular disorders. Derivatives of 1, 4-dihydropyridine are one of the most potent calcium antagonists. In this study four novel 1, 4-dihydropyridine calcium channel blockers were synthesized and their hypotensive properties were investigated in male rats. MATERIALS AND METHODS Four 1, 4-dihydropyridines bearing 1-(4-fluorobenzyl)-5-imidazolyl substituent at 4 position (5a-d) were synthesized and tested for hypotensive activity in male rats. The animal was anaesthetized and the right jugular vein was cannulated for the administration of test agents. The left carotid artery was cannulated and connected to a pressure transducer for continuous monitoring of arterial blood pressure. RESULTS All synthesized compounds lowered rat blood pressure significantly in comparison with DMSO as vehicle and nifedipine as positive control. The hypotensive effects of all compounds were less than that of nifedipine at 2 and 4 mg/kg (P< 0.05). The order of their effects on mean arterial blood pressure (MABP) was 5b>5c>5a>5d at dose of 4 mg/kg (P< 0.05). All compounds tested increased heart rate in comparison with DMSO (P< 0.05). The chronotropic effect of nifedipine was significantly less than synthesized compounds at dose of 4 mg/kg (P< 0.01). CONCLUSION The results showed that these novels 1, 4-dihydropyridines decreased mean arterial blood pressure (MABP) significantly, while increased heart rate in rat.