I have come to the conclusion that vinpocetine should be eradicated from our supplement stashes. This is due in light of evidence brought about by "dopamine" who is now posting more frequently on our boards.
This is taken from M & M, a thread started by dopamine.
Trejo F et al, 2001 reported on the "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings" and found that vinpocetine increases DOPAC release, while simultaneously decreasing vesicular dopamine storage in a similar fashion as reserpine - an indole alkaloid with antipsychotic and antihypertensive properties with some structural similarities to vinpocetine (4). The authors report in the results section that "vinpocetine at increasing concentrations progressively decreases internal DA and increases DOPAC release" and "markedly inhibits DAT-mediated release of endogenous DA." (5)
The effects of vinpocetine on DA and DOPAC levels are not believed to be related to the well-demonstrated inhibitory effects on voltage sensitive Na+ channels, as "vinpocetine increases DOPAC release independently of the state of presynaptic VSSC." A possible MAO-A enhancing mechanism is ruled out "as vinpocetine fails to modify the inhibition of DOPAC formation caused by clorgyline" - a potent inhibitor of MAO-A, "indicating that a reserpine-like mechanism is involved in the vinpocetine-induced increase in DOPAC formation." (6)
If vinpocetine does indeed act in a "reserpine-like" fashion in striatal dopaminergic neurons, one could legitimately raise concern over the use of vinpocetine in otherwise healthy individuals for "cognitive enhancement," as side effects may manifest consistent with reserpine-like side effects, including depression and cognitive dysfunction (7, 8). Because resperine inhibits VMAT-2, the protein primarily responsible for the transportation of monoamines from the cytosol to synaptic vesicles, the amount of dopamine, norepinephrine and serotonin stored in neurons may be substantially decreased pre-synaptically by vinpocetine, leading to a downregulation of monoaminergic tone.
In other words, while vinpocetine may be neuroprotective under some experimental and clinical conditions, it may also interfere with monoamine storage, and affect the way in which the brain responds to drugs acting through dopaminergic, adrenergic, or serotonergic pathways (e.g. amphetamine, modafinil, methylphenidate, cocaine, SSRIs, bupropion, etc). Serious consideration should be given before taking vinpocetine, as it is a highly active pharmacological agent that interacts and interferes with a wide array of brain systems and functions.
1. 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. [abstract]
2. 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. PMID: 15843047. [abstract]
3. "Vinpocetine. Monograph." Alternative Medicine Review 2002 Jun;7(3):240-3, pp. 240. PMID: 12126465. [full text]
4. 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. PMID: 11478921. [abstract]
5. Ibid, pp. 61.
6. Ibid, pp. 64.
7. Huffman JC, Stern TA. "Neuropsychiatric consequences of cardiovascular medications." Dialogues in Clinical Neuroscience 2007;9(1):29-45. PMID: 17506224. [abstract]
8. Cai JX, Ma YY, Xu L, Hu XT. "Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2-adrenergic agonist clonidine." Brain Research 1993 Jun 18;614(1-2):191-6. [abstract]
Then I noticed through researching studies that vinpocetine has a negative impact on the NMDA receptors and the AMPA receptors. These are two very important receptor systems that substances claimed of being nootropics should elicit a positive affect on or no affect at all. Here are two studies which show vinpocetine have a negative affect on them, I THINK!
Kaneko S, Sugimura M, Inoue T, Satoh M.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
The effects of several cerebroprotective and nootropic drugs on the function of excitatory amino acid (EAA) receptor subtypes expressed in Xenopus oocytes after injection of rodent brain poly(A)+ mRNA were investigated. The oocyte response to N-methyl-D-aspartate (NMDA) in the presence of glycine (Gly) was inhibited dose-dependently by bifemelane, indeloxazine, vinpocetine and vincamine while no effect was observed by idebenone, Ca hopantenate, aniracetam or piracetam. Bifemelane, indeloxazine and vinpocetine suppressed the maximum response of NMDA and Gly without affecting their EC50 values. Unlike Mg2+, they did not affect the current-voltage relationship of the NMDA response below 0 mV. On the non-NMDA-type responses of the injected oocytes to kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate (QA), no significant effects were observed by these drugs at 100 microM. On the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine. The dissociation rate of [3H]MK-801 was significantly slowed by Zn2+ and vinpocetine, but not affected by bifemelane or indeloxazine. The Kd value for [3H]MK-801 binding was increased by bifemelane and indeloxazine while Bmax was unchanged. These results suggest that the inhibition of NMDA channels by vinpocetine shows a similarity to the action of Zn2+ which closes the gate of the NMDA channel. In contrast, bifemelane and indeloxazine may affect the phencyclidine (PCP)-site in the open channels and inhibit NMDA function.
PMID: 1652446 [PubMed - indexed for MEDLINE]
AND THIS ONE FOR AMPA
Kiss B, Cai NS, Erdö SL.
Pharmacological Research Centre, Gedeon Richter Ltd., Budapest, Hungary.
The effect of vinpocetine on excitatory amino acid receptors was examined in the rat brain by two different biochemical approaches. In release experiments with striatal slices, vinpocetine reduced the efflux of dopamine and acetylcholine evoked by glutamate, quisqualate and N-methyl-D-aspartate (NMDA), but not that evoked by kainate. In binding experiments with cortical membranes, vinpocetine reduced the binding of [3H]2-amino-3-3-hydroxy-s-methylisoxasole-4-yl-propionic acid ([3H]AMPA), a quisqualate partial agonist, in an incomplete manner, but failed to influence the binding of [3H]kainate and [3H]3-(2-carboxypyperazine-4-yl)-propyl-1-phosphonic acid ([3H]CPP), an NMDA agonist. These findings suggest that vinpocetine is a quisqualate/AMPA antagonist of some specificity and selectivity.
PMID: 1687679 [PubMed - indexed for MEDLINE]
What do you all think? Dopamine, what are your thoughts on the studies I brought up and vinpocetine as a whole for its use in healthy individuals?
edit: I would like to add that I am down to 25mg of tramadol twice daily now. I was doing this just for health (tapering down to get off completely) then yesterday I found out that tramadol is an NMDA antagonist!!!!! No wonder why my memory has been so screwy as of late! Within a few days, I will be off completely. I also got a script for adderall last week, yet I only took a couple pills and decided against taking them. I figure I'd get BETTER, HEALTHIER results by just going about it the NATURAL, HEALTHY way.... This is of course in regards to combating my diagnosed inattentive-type ADD without hyperactivity and most importantly having phenomenal cognitive capabilities indefinitely throughout my immortal lifetime...
Edited by luv2increase, 29 July 2008 - 07:25 PM.