Focus on Vinpocetine

by J. Maslarova, R. Nikolov

Introduction

Ethyl apovincaminate (Vinpocetine) is a vincamine derivative has been used in the clinical practice for over 25 years for the treatment of cerebrovascular disorders and related symptoms. The effects of vinpocetine on cerebral blood flow, brain metabolism, memory functions, and its neuroprotective action have been confirmed in the past years in numerous animal experiments and human studies.
The aim of the present paper is to review the preclinical and clinical studies on vinpocetine.

Pharmacological properties

Vinpocetine exerts a brain neuroprotective effect by a combined action on cerebral circulation, brain metabolism, and rheological properties of the blood. Kiss and Karpati (1996) summarized the pharmacological studies on vinpocetine. Early experiments showed an improvement of the cerebral circulation and oxygen utilization without changes in systemic circulation, cerebral protection in conditions of hypoxia/ischaemia, cognition-enhancing and anticonvulsant activity, and improvement of rheological properties of the blood. Later studies confirmed the above effects and clearly demonstrated a direct neuroprotective action at a cellular level.

Cerebral circulation

· Increases brain perfusion by improvement of cerebral blood flow and decrease of the cerebral vascular resistance in dogs. (Karpati and Szporny, 1976; Szmolenszky and TÖrÖk, 1976);
· Increases the cerebral capillary flow rate in dogs (Szmolenszky and TÖrÖk, 1976)
· Improves total cerebral blood flow in normal conditions and in hypoxic hypoxia in dogs (Bencsáth et al., 1976).

Brain metabolism

· Enhances the cerebral metabolic rate of oxygen in dogs (Karpati and Szporny, 1976);
· Prevents the local cerebral glucose utilization increase, caused by forebrain ischaemia of 10-min duration in rats (Rischke and Krieglstein, 1990).

Neuroprotective action in conditions of hypoxia/ischaemia

· Increases latency to ischemic convulsion in a dose-related manner In a rat model of cerebral ischaemia (bilateral carotid artery occlusion). After 5 days administration (25 mg/kg/day) increases survival time (King and Narcavage, 1986).
· Demonstrates a pronounced protective effect against hypoxia and ischaemia in several animal models (Lamar et al., 1988).
· Increases the local CBF in a model of rat forebrain ischaemia of 10-min duration after 1 h of recirculation (Rischke and Krieglstein, 1991), and at the 7th day after the ischaemia (Rischke and Krieglstein, 1990).
· Increases the neuroprotective effect of adenosine in a model of cytotoxic hypoxia in cultured chick embryo neurons (Krieglstein and Rischke, 1991).
· Reduces the hippocampal neuronal necrosis after pre- or post-ischemic administration in a model of forebrain ischaemia in rats (Rischke and Krieglstein, 1991).
· Exerts a pronounced brain protective effect in doses 5, 10 and 20 mg/kg i.p. in different experimental models of hypoxia/ischaemia (Maslarova and Nikolov, 1999). The effect was similar to nicergoline and weaker than the effect of piracetam.

Biochemical mechanisms

· Vinpocetine showed weaker calcium antagonistic properties in comparison with the effects of flunarizine, verapamil, diltiazem and nimodipine in isolated rabbit basilar and splenic artery (Lamar et al., 1988).
· In binding experiments on rat brain cortical membranes vinpocetine showed properties of a quisqualate/AMPA antagonist of some specificity and selectivity (Kiss et al., 1991).
· Using primary cultures of rat cerebral cortex Lakics et al. (1995) showed that the blockade of voltage-gated sodium channels is a possible mechanism of action for the neuroprotective and anticonvulsant properties of vinpocetine.
· Antioxidant and ROS (reactive oxygen species) scavenging action in conditions in which ROS are excessively generated such as oxidative stress, hypoxia/reoxygenation, ischaemia/reperfusion (Stolc, 1999).
· In vitro studies demonstrated the effect of vinpocetine on Ca2+-calmodulin dependent cGMP-PDE, voltage-operated Ca2+ channels, glutamate receptors and voltage-dependent neuronal Na+ channels (Bonoczk et al., 2000).

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Other effects

· Increases myocardial and renal capillary flow rate in dogs (Szmolenszky and TÖrÖk, 1976).
· Anticonvulsive effect in electroshock and pentylenetetrazole-induced convulsions in mice (Palosi and Szporny, 1976)
· Cognition-enhancing activity in models of scopolamine-induced and hypoxia-induced memory impairment in rats (DeNoble et al., 1986)