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Vinpocetine
Systematic (IUPAC) name
(3α,16α)-Eburnamenine-14-carboxylic acid ethyl ester
Identifiers
CAS number 42971-09-5
ATC code N06BX18
PubChem 5673
Chemical data
Formula C 22H26N2O2  
Mol. mass 350.454 g/mol
Pharmacokinetic data
Bioavailability 56.6 +/- 8.9%
Metabolism hepatic
Half life 2.54 +/- 0.48 hours
Excretion renal
Therapeutic considerations
Pregnancy cat. not recommended
Legal status OTC
Routes 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"),[1] an extract from the periwinkle (plant) Vinca minor.

Vinpocetine is reported to have cerebral blood-flow enhancing[2] and neuroprotective effects,[3] and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment.[4]

Vinpocetine is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory. In other words, Vinpocetine may help support brain functions such as concentration and memory by activating cerebral metabolism. There exists anecdotal report of uncomfortable adverse reactions to vinpocetine in a small subset of users. A low initial dosage is often recommended.

Contents

Controlled clinical trials

As of 2003 only three controlled clinical trials had tested "older adults with memory problems",[5] and these studies had promising results.[5] However, a 2003 Cochrane review concluded that the results were inconclusive.[6]

As of 2003 only one study from 1985[7] had tested young, healthy adults, but this study had only 12 subjects and used a very short treatment period.[5]

Use as a Vasodilator

Vinpocetine widely used in the body building community as an vasodilator. 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.[8] 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.[9]

Vinpocetine is also a phosphodiesterase (PDE) type-1 inhibitor,[10] (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.[11][12]

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.[13] 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.[13]

Side-effects

Side effects of vinpocetine may include indigestion, nausea, dizziness, anxiety, facial flushing, insomnia, headache, drowsiness and dry mouth. Vinpocetine may also cause a temporary drop in blood pressure.[14] In clinical trials adverse effects have been reported infrequently, but the trials were not long-term.[6]

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

Vinpocetine has been implicated in one case to induce agranulocytosis,[15] a condition in which granulocytes, 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.[16]

Other alkaloids extracted from the periwinkle family, including Vincristine and Vinblastine are powerful chemotherapeutic agents which impair formation of microtubules and thus growth of related cancers, intestinal epithelium and bone marrow. The periwinkle family has contributed many powerful drugs to modern medicine however, Vinpocetine needs further testing in the minds of many physicians and researchers before it should be used for any particular purpose. The case of agranulocytosis mentioned above is very concerning from a clinician's standpoint.

Dosage

It is recommended that first-time users ingest only 2–5 mg of vinpocetine with meals to make sure they are not hypersensitive to it. Users may then increase the dosage to 10–40 mg a day (which may, although very rarely, cause some light side-effects).

External links

References

  1. ^ Lörincz C, Szász K, Kisfaludy L (1976). "The synthesis of ethyl apovincaminate". Arzneimittel-Forschung 26 (10a): 1907. PMID 1037211.  
  2. ^ Szilágyi G, Nagy Z, Balkay L, et al. (March 2005). "Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study". Journal of the Neurological Sciences 229-230: 275–84. doi:10.1016/j.jns.2004.11.053. PMID 15760651.  
  3. ^ Dézsi L, Kis-Varga I, Nagy J, Komlódi Z, Kárpáti E (2002). "[Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke]" (in Hungarian). Acta Pharmaceutica Hungarica 72 (2): 84–91. PMID 12498034.  
  4. ^ "Vinpocetine. Monograph". Alternative Medicine Review 7 (3): 240–3. June 2002. PMID 12126465. http://www.thorne.com/altmedrev/.fulltext/7/3/240.pdf.  
  5. ^ a b c McDaniel MA, Maier SF, Einstein GO (2003). "'Brain-specific' nutrients: a memory cure?". Nutrition 19 (11-12): 957–75. doi:10.1016/S0899-9007(03)00024-8. PMID 14624946.  
  6. ^ a b Szatmari SZ, Whitehouse PJ (2003). "Vinpocetine for cognitive impairment and dementia". Cochrane Database of Systematic Reviews (1): CD003119. doi:10.1002/14651858.CD003119. PMID 12535455.  
  7. ^ Subhan Z, Hindmarch I (1985). "Psychopharmacological effects of vinpocetine in normal healthy volunteers". European Journal of Clinical Pharmacology 28 (5): 567–71. doi:10.1007/BF00544068. PMID 3899677.  
  8. ^ Sitges M, Galván E, Nekrassov V (June 2005). "Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes". Neurochemistry International 46 (7): 533–40. doi:10.1016/j.neuint.2005.02.001. PMID 15843047.  
  9. ^ Adám-Vizi V (June 2000). "[Neuroprotective effect of sodium channel blockers in ischemia: the pathomechanism of early ischemic dysfunction]" (in Hungarian). Orvosi Hetilap 141 (23): 1279–86. PMID 10905082.  
  10. ^ Hagiwara M, Endo T, Hidaka H (February 1984). "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle". Biochemical Pharmacology 33 (3): 453–7. doi:10.1016/0006-2952(84)90240-5. PMID 6322804.  
  11. ^ Truss MC, Uckert S, Stief CG, Forssmann WG, Jonas U (1996). "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 24 (3): 129–34. PMID 8839479.  
  12. ^ Gurkovskaia AV, Gokina NI, Buryĭ VA, Shuba MF (January 1987). "[Electrophysiological analysis of the action of kavinton on the smooth muscles]" (in Russian). Biulleten' Eksperimental'noĭ Biologii I Meditsiny 103 (1): 68–71. PMID 3801654.  
  13. ^ a b Trejo F, Nekrassov V, Sitges M (August 2001). "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings". Brain Research 909 (1-2): 59–67. doi:10.1016/S0006-8993(01)02621-X. PMID 11478921.  
  14. ^ http://altmedicine.about.com/od/herbsupplementguide/a/vinpocetine.htm
  15. ^ 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.
  16. ^ The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines, 1st ed. 1998, Integrative Medicine Communications, pub; Bk&CD-Rom edition, 1999.

Vinpocetine
Systematic (IUPAC) name
(3α,16α)-Eburnamenine-14-carboxylic acid ethyl ester
Identifiers
CAS number 42971-09-5
ATC code N06BX18
PubChem CID 5673
Chemical data
Formula C22H26N2O2 
Mol. mass 350.454 g/mol
Pharmacokinetic data
Bioavailability 56.6 +/- 8.9%
Metabolism hepatic
Half-life 2.54 +/- 0.48 hours
Excretion renal
Therapeutic considerations
Pregnancy cat. not recommended
Legal status OTC
Routes 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"),[1] an extract from the periwinkle (plant) Vinca minor.

Vinpocetine is reported to have cerebral blood-flow enhancing[2] and neuroprotective effects,[3] and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment.[4]

Vinpocetine is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory. In other words, Vinpocetine may help support brain functions such as concentration and memory by activating cerebral metabolism. There exists anecdotal report of uncomfortable adverse reactions to vinpocetine in a small subset of users. A low initial dosage is often recommended.

Vinpocetine has been identified as a potent antiinflammatory agent that might have a potential role in the treatment of Parkinson's disease and Alzheimer’s disease[5][6]

Contents

Controlled clinical trials

As of 2003 only three controlled clinical trials had tested "older adults with memory problems",[7] and these studies had promising results[7], in which a 2003 Cochrane review decided that the results were inconclusive.[8]

Prior to 2003, a different study from 1985[9] had tested young, healthy adults, but this study had 12 subjects and used a short treatment period.[7]

Use as a Vasodilator

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

Anti-inflammatory action

Vinpocetine has been identified as a novel antiinflammatory agent.[5][6] Vinpocetine inhibits the up-regulation of NF-κB by TNFα in various cell tests. Reverse transcription polymerase chain reaction also shows that it reduced the TNFα-induced expression of the mRNA of proinflammatory molecules such as interleukin-1 beta, monocyte chemoattractant protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1). In mice, vinpocetine reduced lipopolysaccharide inoculation induced polymorphonuclear neutrophil infiltration into the lung.[5][6] Neuroinflammatory processes can result in neuronal death in Parkinson's disease (PD) and Alzheimer’s disease (AD). It has been suggested that "It would be interesting to test whether vinpocetine’s antiinflammatory properties would have a protective effect in models of neurodegenerative conditions such as AD and PD.".[6]

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.[10] 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.[11]

Vinpocetine is also a phosphodiesterase (PDE) type-1 inhibitor,[12] (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.[13][14]

Independent of vinpocetine's action on PDE, Vinpocetine inhibits IKK preventing IκB degradation and the following translocation of NF-κB to the cell nucleus.[5][6]

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.[15] Such an effect is consistent with the biogenic pharmacology of reserpine, a structural relative of vinpocetine, which depletes catecholamine levels and causes depression as a side effect of the cardiovascular and anti-psychotic effects.[15] However, this effect tends to be reversible upon cessation of Vinpocetine administration, with full remission typically occurring within 3–4 weeks.

Side effects

Side effects of vinpocetine may include indigestion, nausea, dizziness, anxiety, facial flushing, insomnia, headache, drowsiness and dry mouth. Vinpocetine may also cause a temporary drop in blood pressure.[16] In clinical trials adverse effects have been reported infrequently, but the trials were not long-term.[8]

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

Vinpocetine has been implicated in one case to induce agranulocytosis,[17] a condition in which granulocytes, 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.[18]

Other alkaloids extracted from the periwinkle family, including Vincristine and Vinblastine are powerful chemotherapeutic agents which impair formation of microtubules and thus growth of related cancers, intestinal epithelium and bone marrow. The periwinkle family has contributed many powerful drugs to modern medicine however, Vinpocetine needs further testing in the minds of many physicians and researchers before it should be used for any particular purpose.[citation needed] The case of agranulocytosis mentioned above is very concerning from a clinician's standpoint.

Dosage

It is recommended that first-time users ingest only 2–5 mg of vinpocetine with meals to make sure they are not hypersensitive to it. Users may then increase the dosage to 10–40 mg a day (which may, although very rarely, cause some light side effects).

External links

References

  1. ^ Lörincz C, Szász K, Kisfaludy L (1976). [Expression error: Unexpected < operator "The synthesis of ethyl apovincaminate"]. Arzneimittel-Forschung 26 (10a): 1907. PMID 1037211. 
  2. ^ Szilágyi G, Nagy Z, Balkay L, et al. (2005). [Expression error: Unexpected < operator "Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study"]. Journal of the Neurological Sciences 229-230: 275–84. doi:10.1016/j.jns.2004.11.053. PMID 15760651. 
  3. ^ Dézsi L, Kis-Varga I, Nagy J, Komlódi Z, Kárpáti E (2002). [Expression error: Unexpected < operator "[Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke]"] (in Hungarian). Acta Pharmaceutica Hungarica 72 (2): 84–91. PMID 12498034. 
  4. ^ "Vinpocetine. Monograph". Alternative Medicine Review 7 (3): 240–3. 2002. PMID 12126465. http://www.thorne.com/altmedrev/.fulltext/7/3/240.pdf. 
  5. ^ a b c d Jeon, KI; Xu, X; Aizawa, T; Lim, JH; Jono, H; Kwon, DS; Abe, J; Berk, BC et al. (2010). [Expression error: Unexpected < operator "Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism."]. Proceedings of the National Academy of Sciences of the United States of America 107 (21): 9795–800. doi:10.1073/pnas.0914414107. PMID 20448200. 
  6. ^ a b c d e Medina, AE (2010). [Expression error: Unexpected < operator "Vinpocetine as a potent antiinflammatory agent."]. Proceedings of the National Academy of Sciences of the United States of America 107 (22): 9921–2. doi:10.1073/pnas.1005138107. PMID 20495091. 
  7. ^ a b c McDaniel MA, Maier SF, Einstein GO (2003). [Expression error: Unexpected < operator "'Brain-specific' nutrients: a memory cure?"]. Nutrition 19 (11-12): 957–75. doi:10.1016/S0899-9007(03)00024-8. PMID 14624946. 
  8. ^ a b Szatmari SZ, Whitehouse PJ (2003). [Expression error: Unexpected < operator "Vinpocetine for cognitive impairment and dementia"]. Cochrane Database of Systematic Reviews (1): CD003119. doi:10.1002/14651858.CD003119. PMID 12535455. 
  9. ^ Subhan Z, Hindmarch I (1985). [Expression error: Unexpected < operator "Psychopharmacological effects of vinpocetine in normal healthy volunteers"]. European Journal of Clinical Pharmacology 28 (5): 567–71. doi:10.1007/BF00544068. PMID 3899677. 
  10. ^ Sitges M, Galván E, Nekrassov V (2005). [Expression error: Unexpected < operator "Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes"]. Neurochemistry International 46 (7): 533–40. doi:10.1016/j.neuint.2005.02.001. PMID 15843047. 
  11. ^ Adám-Vizi V (2000). [Expression error: Unexpected < operator "[Neuroprotective effect of sodium channel blockers in ischemia: the pathomechanism of early ischemic dysfunction]"] (in Hungarian). Orvosi Hetilap 141 (23): 1279–86. PMID 10905082. 
  12. ^ Hagiwara M, Endo T, Hidaka H (1984). [Expression error: Unexpected < operator "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle"]. Biochemical Pharmacology 33 (3): 453–7. doi:10.1016/0006-2952(84)90240-5. PMID 6322804. 
  13. ^ Truss MC, Uckert S, Stief CG, Forssmann WG, Jonas U (1996). [Expression error: Unexpected < operator "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 24 (3): 129–34. PMID 8839479. 
  14. ^ Gurkovskaia AV, Gokina NI, Buryĭ VA, Shuba MF (1987). [Expression error: Unexpected < operator "[Electrophysiological analysis of the action of kavinton on the smooth muscles]"] (in Russian). Biulleten' Eksperimental'noĭ Biologii I Meditsiny 103 (1): 68–71. PMID 3801654. 
  15. ^ a b Trejo F, Nekrassov V, Sitges M (2001). [Expression error: Unexpected < operator "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings"]. Brain Research 909 (1-2): 59–67. doi:10.1016/S0006-8993(01)02621-X. PMID 11478921. 
  16. ^ "Vinpocetine - What You Need to Know About Vinpocetine". Altmedicine.about.com. http://altmedicine.about.com/od/herbsupplementguide/a/vinpocetine.htm. Retrieved 2010-07-29. 
  17. ^ Shimizu Y, Saitoh K, Nakayama M, et al. Agranulocytosis induced by vinpocetine. Medicine Online, Retrieved March 08, 2008.
  18. ^ The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines, 1st ed. 1998, Integrative Medicine Communications, pub; Bk&CD-Rom edition, 1999.[page needed]








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