Clinical and non-clinical investigations using positron emission tomography, near infrared spectroscopy and transcranial Doppler methods on the neuroprotective drug vinpocetine: a summary of evidences.
Vinpocetine (Cavinton, Gedeon Richter, Budapest) is widely used as a neuroprotective drug in the prevention and treatment of cerebrovascular diseases. Vinpocetine is a potent inhibitor of the voltage-dependent Na(+) channels and a selective inhibitor of the Ca(2+)/caldmoduline-dependent phosphodiesterase 1. The clinical efficacy has been supported by several previous studies. Positron emission tomography (PET) is a powerful method to evaluate the fate, the site of action, the pharmacological and physiological effects of a drug in the brain and other organs. We have demonstrated in monkey that the [11C]-labelled vinpocetine rapidly enters the brain after intravenous (i.v.) injection, the maximal uptake being approximately 5% of the total injected radioactivity. The distribution pattern of vinpocetine in the brain was heterogenous, with the highest uptake in the thalamus, basal ganglia and visual cortex. These findings were confirmed in healthy humans, where the i.v. administered [11C]-labelled vinpocetine had a similar distribution pattern. The highest uptake in the brain was 3.71% of the total administered radioactivity. Quite recently, we have shown that [11C]-labelled vinpocetine administered orally to healthy human volunteers also rapidly appears in the brain and shows a similar distribution pattern, the highest uptake being 0.71% of the total administered radioactivity. In two separate sets of clinical studies where chronic ischaemic post-stroke patients were either treated with a single infusion (Study 1) or with daily vinpocetine infusion for 2 weeks (Study 2), we have shown that vinpocetine increases the regional cerebral glucose uptake and to a certain extent glucose metabolism in the so-called peri-stroke region as well as in the relatively intact brain tissue. The 2-week-long treatment also increased the regional cerebral blood flow (CBF) especially in the thalamus, basal ganglia and visual cortex of the nonsymptomatic hemisphere. We have demonstrated the cerebral perfusion-enhancing and parenchymal oxygen extraction-increasing effects of vinpocetine in subacute ischaemic stroke patients by near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) methods.
Vas
Adám
A
Chemical Works of Gedeon Richter Limited, H-1103 Budapest, Gyömrõi út 19/21 P.O.B. 27, Budapest 1103, Hungary. a.vas@richter.hu
Gulyás
Balázs
B
Szabó
Zsolt
Z
Bönöczk
Péter
P
Csiba
László
L
Kiss
Béla
B
Kárpáti
Egon
E
Pánczél
Gyula
G
Nagy
Zoltán
Z
D000368:Aged; D000818:Animals; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D002986:Clinical Trials as Topic; D006801:Humans; D008252:Macaca fascicularis; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019265:Spectroscopy, Near-Infrared; D014055:Tomography, Emission-Computed; D017585:Ultrasonography, Doppler, Transcranial; D014748:Vinca Alkaloids / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D014748:Vinca Alkaloids; C013983:vinpocetine