Vinpocetine

Drugbox
IUPAC_name = (3α,16α)-Eburnamenine-14-carboxylic acid ethyl ester


width = 173px
CAS_number=42971-09-5
ATC_prefix=N06
ATC_suffix=BX18
ATC_supplemental=
PubChem=5673
DrugBank=
C = 22 | H = 26 | N = 2 | O = 2
molecular_weight = 350.454 g/mol
bioavailability= 56.6 +/- 8.9%
metabolism = hepatic
distribution = 2.1 l/kg
clearance rate = 0.366 l/h/kg
elimination_half-life = 2.54 +/- 0.48 hours
excretion = renal
time to max plasma concentration = 1-1.5 h
pregnancy_category = not recommended
legal_status = OTC
routes_of_administration= oral, intravenous

Vinpocetine (brand names: Cavinton, Intelectol; chemical name: ethyl apovincaminate) is a semisynthetic derivative alkaloid of vincamine (sometimes described as "a synthetic ethyl ester of apovincamine"), [Lörincz C, Szász K, Kisfaludy L. "The synthesis of ethyl apovincaminate." "Arzneimittel-forschung" 1976;26(10a):1907. PMID: 1037211. ] an extract from the periwinkle (plant) "Vinca minor."

Vinpocetine is reported to have cerebral blood-flow enhancing [Szilágyi G, Nagy Z, Balkay L, Boros I, Emri M, Lehel S, Márián T, Molnár T, Szakáll S, Trón L, Bereczki D, Csiba L, Fekete I, Kerényi L, Galuska L, Varga J, Bönöczk P, Vas A, Gulyás B. "Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study." "Journal of Neurological Sciences" 2005 Mar 15;229-230:275-84. Epub 2005 Jan 8. PMID: 15760651.] and neuroprotective effects, [Dézsi L, Kis-Varga I, Nagy J, Komlódi Z, Kárpáti E. " [Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke] ." "Acta Pharmaceutica Hungarica" 2002;72(2):84-91. [http://www.ncbi.nlm.nih.gov/pubmed/12498034 12498034] ] and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment. ["Vinpocetine. Monograph." "Alternative Medicine Review" 2002 Jun;7(3):240-3, pp. 240. PMID: 12126465.]

Vinpocetine is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory. There exists anecdotal report of uncomfortable adverse reactions to vinpocetine in a small subset of users. A low initial dosage is often recommended.

Possible Nootropic Properties

A number of studies on healthy volunteers have demonstrated vinpocetine may elicit improvement on some aspects of memory. [ Psychopharmacological effects of vinpocetine in normal healthy volunteers [http://www.springerlink.com/content/jn46808130509x42/] .] [ Possible memory-enhancing properties of vinpocetine [http://www3.interscience.wiley.com/journal/109670811/abstract] .] The degree which the nootropic effects of vinpocetine are mediated by mechanisms beyond vasodilation is currently unknown.

Use as a Vasodilator

Vinpocetine widely used in the body building community as an antivasoconstrictor. However, no studies have been conducted on the effectiveness of vinpocetine on performance enhancement during exercise.

Mechanism of Action

Vinpocetine has been shown to selectively inhibit voltage-sensitive Na+ channels, resulting in a dose-dependent decrease in evoked extracellular Ca+ ions in striatal nerve endings. [Sitges M, Galván E, Nekrassov V. "Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes." "Neurochemistry International" 2005 Jun;46(7):533-40. [http://www.ncbi.nlm.nih.gov/pubmed/15843047 PMID: 15843047.] ] The Na+ channel inhibiting properties of vinpocetine are thought to contribute to a general neuroprotective effect through blockade of excitotoxicity and attenuation of neuronal damage induced by cerebral ischemia/reperfusion. [Adám-Vizi V. " [Neuroprotective effect of sodium channel blockers in ischemia: the pathomechanism of early ischemic dysfunction] ." "Orvosi Hetilap" 2000 Jun 4;141(23):1279-86. [http://www.ncbi.nlm.nih.gov/pubmed/10905082 PMID: 10905082] ]

Vinpocetine is also a phosphodiesterase (PDE) type-1 inhibitor, [Hagiwara M, Endo T, Hidaka H. "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle." Biochemical Pharmacology 1984 Feb 1;33(3):453-7. PMID: 6322804.] (with an IC₅₀ of approximately 10^-5 M.) leading to increases in intracellular levels of cyclic guanosine 3'5'-monophosphate (cGMP), an action that has been attributed to the vasorelaxant effects of vinpocetine on cerebral smooth muscle tissue. [Truss MC, Uckert S, Stief CG, Forssmann WG, Jonas U. "Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. II. Effect of various PDE inhibitors on smooth muscle tone and cyclic nucleotide levels in vitro." "Urological Research" 1996;24(3):129-34. PMID: 8839479.] [Gurkovskaia AV, Gokina NI, Buryĭ VA, Shuba MF. " [Electrophysiological analysis of the action of kavinton on the smooth muscles] ." Biull Eksp Biol Med. 1987 Jan;103(1):68-71. PMID: 3801654. ]

Increases in neuronal levels of DOPAC, a metabolic breakdown product of dopamine, have been shown to occur in striatal isolated nerve endings as a result of exposure to vinpocetine. [Trejo F, Nekrassov V, Sitges M. "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings." "Brain Research" 2001 Aug 3;909(1-2):59-67. [http://www.ncbi.nlm.nih.gov/pubmed/11478921 PMID: 11478921] .] Such an effect is consistent with the biogenic pharmacology of reserpine, a structural relative of vinpocetine, which depletes catecholamine levels and may cause depression as a side-effect of the cardiovascular and anti-psychotic effects. [Ibid.]

ide-effects

No adverse reactions to vinpocetine have been reported in human trials. Due to the small sample size of existing trials the prevalence of adverse reactions is still unknown although thought to be rare. Anecdotal evidence has suggested that a small subset of users may experience adverse reactions. Due to the possibility of adverse reactions, a low initial dose is typically recommended. The small size of existing studies precludes conclusion on the prevalence or severity of possible adverse reactions in vinopocetine usage.

The safety of vinpocetine in pregnant women has not been evaluated.

Vinpocetine has been implicated in one case to induce agranulocytosis, [Shimizu Y, Saitoh K, Nakayama M, et al. Agranulocytosis induced by vinpocetine. Medicine Online [serial online] . Available at: http://www.priory.com/med/vinpocetine.htm. Accessed March 08, 2008.] a condition in which granulocytyes - an important type of white blood cell, are markedly decreased. Some people have anecdotally noted that their continued use of vinpocetine reduces immune function. Commission E warned that vinpocetine reduced immune function and could cause apoptosis in the long term. ["The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines", 1st ed. 1998, Integrative Medicine Communications, pub; Bk&CD-Rom edition, 1999. ]

Dosage

It is recommended that first-time users ingest only 2-5 mg of vinpocetine to make sure they are not hypersensitive to it. Users may then increase the dosage to 10-30 mg a day (which may, although very rarely, cause some side-effects).

External links

* [http://www.erowid.org/smarts/vinpocetine/ Erowid Vinpocetine Vault]
* [http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/vin_0259.shtml Vinpocetine article from PDRhealth]
* [http://www.cochrane.org/reviews/en/ab003119.html Vinpocetine for cognitive impairment and dementia] - Cochrane review

References