Pharmacology of Nimodipine

Abstract

The major pharmacological findings with nimodipine reviewed in this chapter are summarized in TABLE 3. On the basis of these findings, the following conclusions appear to be justified: 1. Nimodipine is a 1,4-dihydropyridine with Ca2+ channel antagonist properties. It is more lipophilic than nifedipine and its distribution volume in the brain of rats is higher than that of nifedipine. 2. Nimodipine dilates cerebral vessels at considerably lower concentrations than required for dilatation of peripheral blood vessels. It can, therefore, improve cerebral blood flow at doses that do not reduce systemic arterial pressure. 3. Nimodipine inhibits 45Ca uptake into vascular smooth muscle and neuronal cells. 4. Nimodipine antagonized postischemic cerebral hypoperfusion in cats and prolonged life of stroke-prone spontaneously hypertensive (SH) rats at doses that have little if any effect on arterial blood pressure. 5. Nimodipine reduced neurological deficits in dogs and monkeys with global cerebral ischemia. In focal ischemia (MCA occlusion) nimodipine reduced infarct size and neurological deficits and normalized intracellular brain pH. 6. In addition to its cerebral vasodilator effect, nimodipine appears to have a direct neuronal action. The suggested evidence for the neuronal site of action of nimodipine includes: a. Presence of nimodipine binding sites in brain. b. Blockade by nimodipine of Ca2+ channels in single nerve cells and in endocrine cells under conditions of sustained depolarization. c. Interactions with centrally acting drugs. d. Effects on release of various neurotransmitters from neuronal tissue or endocrine cells. e. Demonstration of anticonvulsant action of nimodipine. f. Blockade of behavioral effects of Ca2+ channel agonists by calcium channel antagonists.

Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE)

“…It improves cerebral perfusion after acute ischemia [26] and reduces neurological deficits [27-29]. It has specific affinity for receptor operated calcium channels in cerebral vessels and for specific membrane-located receptor sites that may be associated with the pharmacological action of nimodipine in the brain [30,31].…”

“…However, a series of chain reactions induce a large amount of neuronal damage at acute and subacute stages of stroke [36]. Theoretically, nimodipine could have clinical benefits due to its ability to modulate blood vessels and protect neurons, especially its probable ability to regulate the capillary with relatively intact structure and functions in the severely injured brain [27,30,37,38]. It is thus conceivable that it is clinically beneficial to begin nimodipine therapy at early stage after the stroke.…”

The therapeutic effects of melatonin and nimodipine in rats after cerebral cortical injury

“…Traumatic brain injury (TBI) occurs through primary and secondary mechanisms. Primary brain injury is generally associated with cerebral contusions, hematomas and diffuse axonal injuries at the time of the traumatic insult (23,30). Secondary brain injury occurs due to the excess release of the excitatory aminoacids and neuromediators aspartate and glutamate, increased intracellular calcium, the activation of arachidonic acid cascade, and eventually the induction of lipid peroxidation via the formation of free oxygen radicals (3,14,19,34).…”

“…Since melatonin is a lipophilic enzyme, it does not need a specific binding site or a receptor on the cell membrane. Nimodipine is a calciumchannel blocker and since it is highly-lipophilic, it can easily penetrate into the central nervous system in considerable amount (30,37). Nimodipine has more influence on voltagegated Ca2+ channels and these particular channels are more abundant in brain.…”

Effects of Nimodipine on Brain Blood Flow following Acute Brain Ischemia in the Newborn Piglet

“…[2][3][4]. Calcium channel blockers, such as nimodipine, have been shown to be efficacious in improving postischemic brain injury and mortality in adult humans and in animal models [5,6], Despite its promise of reducing brain damage in the adult, there are few ani mal studies of nimodipine in fetal or newborn animals. Nimodipine, a dihydropyridine, has enhanced lipid solubility which gives potent cerebral vasodilatory activity [7], We have developed an animal model, severe pneumo thorax (SP) in the piglet which closely paral lels the clinical events of a tension pneumo thorax in the infant.…”