Nicardipine: A Hypotensive Dihydropyridine-Type Calcium Antagonist with a Peculiar Cerebrovascular Profile

Abstract

Control of blood pressure protects against the development of cerebrovascular lesions, stroke, and vascular dementia (VaD). Cerebrovascular disease is increasingly recognized as a cause of cognitive impairment and dementia primarily in the elderly. Nicardipine is a dihydropyridine-type calcium channel blocker (CCB) with a peculiar cerebrovascular profile developed approximately 30 years ago. This study has reviewed the main controlled clinical studies investigating the use of nicardipine in pathologies associated with cerebrovascular injury, such as subarachnoid haemorrhage (SAH), acute stroke, and VaD. SAH is a main cerebrovascular indication of CCBs. In this indication, CCBs prevent vasospasm and improve clinical outcomes. Nimodipine represents the CCB more investigated in this indication. Former studies did not demonstrate a clear advantage of nicardipine versus nimodipine in SAH. A more recent approach using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits, and improved clinical outcome after severe SAH. Controlled trials have shown the effectiveness of the drug in preventing stroke. Increasing evidence suggests some benefit of some CCBs in VaD or mixed degenerative and vascular dementia. In this setting, nicardipine has been investigated in approximately 6,000 patients, with an improvement of cognitive deterioration in more than 60% of patients treated. The pronounced anti-hypertensive activity of nicardipine and its safety and effectiveness in cognitive domain suggest its reconsideration in the treatment of cognitive impairment of vascular origin as well as for reducing the risk of recurrent stroke in patients at high risk of it.

Control of basal autophagy by calpain1 mediated cleavage of ATG5

“…We have previously carried out a high-throughput image-based screen and identified 7 FDA-approved drugs which can induce autophagy without inducing cell death 5. Interestingly, five of the seven compounds were previously known to have activity in inhibiting intracellular Ca2+ 6–10…”

Anti-Neuroinflammatory Effects of the Calcium Channel Blocker Nicardipine on Microglial Cells: Implications for Neuroprotection

“…The protective effects of nimodipine have been evidenced by animal models of ischemic brain [64]. Previous studies have also reported that nicardipine can protect against hypertension-related brain damage [32]–[34]. Nifedipine has been reported to inhibit the expression of inflammatory and fibrogenic responses in advanced glycation end product-exposed fibroblasts [65].…”

“…In clinical practice, nicardipine has also been used for the treatment of acute hypertension in acute brain disease, with promising outcomes [26], [28]–[31]. Previous studies also reported neuroprotective effects of nicardipine on hypertension-induced brain damage [32]–[34]. Few animal and human studies have assessed the beneficial use of nicardipine in acute ischemic stroke [35].…”

Treatment of Vascular Cognitive Impairment

“…A large trial assessing the benefit of nimodipine in preventing cognitive decline following acute ischemic stroke is ongoing [56]. Nicardipine has been shown to slow the progression of cognitive decline in several trials [57]. In one RCT, nicardipine given at a dose of 20 mg three times a day for a year delayed the rate of cognitive decline in subjects with VaD [58].…”