Mechanism of action of
Kiss B, Karpati E.
Richter Gedeon Vegyeszeti Gyar
Farmakologiai Kutato Kozpont, Budapest
Acta Pharm Hung 1996 Sep;66(5):213-24
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
(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,
(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.