Mechanism of action of Nicardipine

Nicardipine is a dihydropyridine-type CCB with highvascular selectivity，strong antihypertensive activity andcerebrovascular effects.Nicardipineprotects from atherogenesis in experimental vascular injury; has antioxidant effects, pre-venting endothelial cell damage from free radical injury and inhibits platelet aggregation. 

Mechanism of action

Nicardipine,like all CCBs, lowers arterial pres-sure by reducing peripheral vascular resistance，therebydecreasing both systolic and diastolic BP and improvingmyocardial oxygen supply by vasodilating coronary arteries.Therefore,nicardipine is an anti-angina and cardioprotective agent.CCBs are more effective in BP lowering in patientsolder than 55 years or those of black ethnic origin at anyage.Amenta et al.(2009) recommendnicardipine for the treatment of hypertension after acuteischaemic stroke or intracerebral haemorrhage for the con-trol of vasospasm in SAH, as well as for stroke prevention. 

Amenta et al.(2009) reviewed the effects of nicardipineon cognition in 24 studies performed primarily in Japan,Spain and Italy on about 6000 patients with 'chronic cere-brovascular insufficiency' due to several forms of CVDincluding PSD and ranging in severity from vascular MCIto VaD. Positive effects of treatment with nicardipine wereobserved in over 60% of patients; more favourable resultsoccurred in hypertensive patients resulting in decreasedsystolic and diastolic BP, improvement of neurologicalsymptoms and signs，as well as amelioration of cognitionassessed with the SCAG scale,MMSE and other batteries.

Related research

The Spanish Group of Nicardipine Study in VaD conducted a dou-ble-blind, placebo-controlled RCT to investigate the effectof nicardipine on cognitive function in patients with VaD.'The effect of daily treatment with nicardipine (20 mg threetimes per day) for 1 year was investigated in 156 patientswith cognitive impairment of vascular origin,random-ized to nicardipine (N = 8l) or placebo (N = 75).A total of142 subjects completed the study (nicardipine N = 73, pla-cebo N = 60) on intention-to-treat analysis.The primaryefficacy variable was the loss of >10% of the MMSE basalscore; other end points were the Short Portable MentalStatus Questionnaire (SPMSQ) score, func-tional disability and drug safety.

At 1 year, 21.1% of patientstreated with nicardipine had lowered the MMSE score ver-sus 34.6% with placebo. Favourable effects of nicardipinewere found on females (40.9% versus 10.5%, p = 0.01876),previously untreated subjects (46.2%versus 13.3%，p =0.00748) and patients on concomitant antiplatelet treat-ment (35.0% versus 15.9, p = 0.03836).Survival analysisfound patients on nicardipine took longer to lose cognitivecapacities (p = 0.031,RR 1.15-3.99).In summary, nicardip-ine significantly delayed cognitive decline, producing betterevolution in females.'The drug was remarkably safe and waswell tolerated for 1 year; side effects secondary to vasodila-tation were short lived and of low intensity.

The largest (N = 6375 patients) nicardipine trial on vas-cular MCI and VaD was an open, prospective,multicen-tre,6-month study to test the efficacy and tolerability ofa single 40 mg/day oral dose of nicardipine retard (slowrelease) in patients with cognitive deterioration of vas- cular origin.BP,ADLs and cognition with the SPMSQ score were obtained. Nicardipine improved functional capac- ity in 65.5% of the patients; systolic/diastolic BP decreased11.3/7.4 mm Hg in hypertensive patients treated withother antihypertensive drugs and 5.9/4.3 mm Hg in those not taking antihypertensives. Nicardipine was well toleratedand no major side effects were seen.

Based on this evidence, Amenta et al. con-cluded that the anti-hypertensive effect of nicardipine, itssafety and effectiveness in improving cognition and func-tional domains make this a recommended drug in the treat-ment of cognitive impairment of vascular origin.