Nimodipine and Its Use in Cerebrovascular Disease: Evidence from Recent Preclinical and Controlled Clinical Studies

Abstract

Nimodipine is a 1,4-dihydropyridine-derivative Ca²⁺-channel blocker developed approximately 30 years ago. It is highly lipophilic, crosses the blood-brain barrier, and reaches brain and cerebrospinal fluid. Early treatment with nimodipine reduces the severity of neurological deficits resulting from vasospasm in subarachnoid haemorrhage (SAH) patients. In SAH, nimodipine reduced spasm-related deficits of all severities, but no spasm-unrelated deficits. This paper has reviewed preclinical studies on the influence of nimodipine in various animal models of cerebral ischemia, with particular attention toward investigations published in the last 10 years. These studies further support the main indication of nimodipine, by clarifying some mechanisms of the anti-ischemic activity of the compound. Papers reporting a possible role of nimodipine in epileptogenesis were also examined. Clinical studies on nimodipine were grouped into subarachnoid hemorrhage, acute ischemic stroke, cerebral ischemia without stroke, dementia disorders, and migraine. Clinical investigations have shown that the drug improves neurological outcome by reducing the incidence and severity of ischemic deficits in patients with SAH from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition. No relevant effects of treatment with nimodipine were reported for acute ischemic stroke, cerebral ischemia without stroke, and migraine, except than for cluster headache. The less pronounced cardiovascular effects of nimodipine compared to other dihydropyridine-type Ca²⁺-channel blockers probably accounts for its use out of label for treating patients affected by chronic cerebral ischemia and vascular cognitive impairment. However, the blood pressure-lowering effects of nimodipine should not be minimized, as clinical studies have documented lowering blood pressure in small groups of patients, including cases of withdrawn due to pronounced hypotension induced by nimodipine administration. In the area of vascular cognitive impairment, short-term benefits of nimodipine do not justify its use as a long-term anti-dementia drug, and benefits obtained in elderly patients affected by subcortical vascular dementia require to be confirmed by other groups and in larger scale trials. In conclusion, nimodipine is a safe drug with an important place in pharmacotherapy and with the main documentation for reduction in the severity of neurological deficits resulting from vasospam in SAH patients.

Keywords:

• nimodipine
• calcium channel
• subarachnoid haemorrhage
• brain ischemia
• clinical use