[Mechanism of action of vinpocetine].
Cavinton was introduced into the clinical practice some twenty years ago in Hungary for the treatment of cerebrovascular disorders and related symptoms. Since then, its active ingredient, vinpocetine, beside its therapeutical utilization, has become a reference compound in the pharmacological research of cognitive deficits caused by hypoxia and ischaemia as well as in the cellular and biochemical investigations related to cyclic nucleotides. In this review a survey is given on the experimental data obtained with vinpocetine and an attempt is made to outline the drug's mechanism of action. Early experiments with vinpocetine indicated five main pharmacological and biochemical actions: (1) selective enhancement of the brain circulation and oxygen utilization without significant alteration in parameters of systemic circulation, (2) increased tolerance of the brain toward hypoxia and ischemia, (3) anticonvulsant activity, (4) inhibitory effect on phosphodiesterase (PDE) enzyme and (5) improvement of rheological properties of the blood and inhibition of aggregation of thrombocytes. Later studies in various laboratories confirmed the above effects and clearly demonstrated that vinpocetine offers significant and direct neuroprotection both under in vitro and in vivo conditions. Evidence has been obtained that neuroprotective action vinpocetine is related to the inhibition of operation of voltage dependent neuronal Na(+)-channels, indirect inhibition of some molecular cascades initiated by the rise of intracellular Ca(2+)-levels and, to a lesser extent, inhibition of adenosine reuptake. Vinpocetine has been shown to be selective inhibitor of Ca(2+)-calmodulin dependent cGMP-PDE. It is assumed that this inhibition enhances intracellular a GMP levels in the vascular smooth muscle leading to reduced resistance of cerebral vessels and increase of cerebral flow. This effect might also beneficially contribute to the neuroprotective action.
Kiss
B
B
Richter Gedeon Vegyészeti Gyár Rt., Farmakológiai Kutató Központ, Budapest.
Kárpáti
E
E
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D015222:Sodium Channels; D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C013983:vinpocetine; D002118:Calcium
Vinpocetin hatásai, hatásmechanizmusa.