From Wikipedia, the free encyclopedia
receptors (or P1 receptors) are a class of , [] with
In humans, there are four types of adenosine receptors. Each is encoded by a separate gene and has different functions, although with some overlap. For instance, both A1 receptors and A2A play roles in the heart, regulating
oxygen consumption and
blood flow, while the A2A receptor also has broader anti-inflammatory effects throughout the body. These two receptors also have important roles in the brain, regulating the release of other
and , while the A2B and A3 receptors are located mainly peripherally and are involved in processes such as inflammation and immune responses.
Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist
being used in hospitals as treatment for severe
(rapid heart beat), and acting directly to slow the heart through action on all four adenosine receptors in heart tissue, as well as producing a
effect through action on A1 and A2A receptors in the brain.
derivatives such as
act as non-selective
at A1 and A2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a
effect and rapid heart rate. These compounds also act as , which produces additional
effects, and makes them medically useful for the treatment of conditions such as , but less suitable for use in scientific research.
Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research.
Adenosine receptors
Antagonists
Inhibition
↓ vesicle release
Afferent arteriolar constriction in Kidney
N6-3-methoxyl-4-hydroxybenzyl adenine riboside (B2)
SDZ WAG 994
Decreased dopaminergic activity in CNS
Inhibition of central neuron excitation.
N6-3-methoxyl-4-hydroxybenzyl adenine riboside (B2)
Also recently discovered A2B has Gq →
→ Release calcium → activate calmodulin → activate myosin light chain kinase → phosphrylate myosin light chain → myosin light chain plus actin → bronchoconstriction[]
bronchospasm
5'-N-ethylcarboxamidoadenosine
theophylline
Cardiac muscle relaxation
Smooth muscle contraction
cardioprotective in
inhibition of neutrophil
2-(1-Hexynyl)-N-methyladenosine
CF-101 (IB-MECA)
2-Cl-IB-MECA
theophylline
MRE3008F20
Main article:
The adenosine A1 receptor has been found to be ubiquitous throughout the entire body.
This receptor has an inhibitory function on most of the tissues in which it is expressed. In the brain, it slows metabolic activity by a combination of actions. Presynaptically, it reduces
release while post synaptically it has been found to stabilize the magnesium on the .
Specific A1
(DPCPX), and Cyclopentyltheophylline (CPT) or 8-cyclopentyl-1,3-dipropylxanthine (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine ().
The A1, together with A2A receptors of endogenous adenosine play a role in regulating
oxygen consumption and coronary blood flow. Stimulation of the A1 receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing
cell function, resulting in a decrease in . This makes adenosine a useful medication for treating and diagnosing , or excessively fast heart rates. This effect on the A1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid
push during . The rapid infusion causes a momentary myocardial stunning effect.
In normal physiological states, this serves as protective mechanisms. However, in altered cardiac function, such as
caused by ,
caused by , adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion.
Adenosine antagonists
Because a reduction in A1 expression appears to prevent hypoxia-induced
and loss of white matter and therefore raise the possibility that pharmacological blockade of A1 may have clinical utility.
Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants.
Main article:
As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow.
The activity of A2A adenosine receptor, a G-protein coupled receptor family member, is mediated by G proteins that activate adenylyl cyclase. It is abundant in basal ganglia, vasculature and platelets and it is a major target of caffeine.
The A2A receptor is responsible for regulating myocardial blood flow by
the , which increases blood flow to the , but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.
Specific antagonists include
(KW-6002) and SCH-58261, while specific agonists include
and ATL-146e.
Main article:
This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation.
Main article:
It has been shown in studies to inhibit some specific signal pathways of adenosine. It allows for the inhibition of growth in human melanoma cells. Specific antagonists include MRS1191, MRS1523 and MRE3008F20, while specific agonists include
and MRS3558.
Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M (1997). "Towards a revised nomenclature for P1 and P2 receptors". Trends Pharmacol. Sci. 18 (3): 79–82. :.  .
Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001). . Pharmacol. Rev. 53 (4): 527–52.  .
Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479–92. :.  .
Haskó G, Pacher P (March 2008). . Journal of Leukocyte Biology 83 (3): 447–55. :.  .  .
Kalda A, Yu L, Oztas E, Chen JF (October 2006). "Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson's disease". Journal of the Neurological Sciences 248 (1–2): 9–15. :.  .
Fuxe K, Ferré S, Genedani S, Franco R, Agnati LF (September 2007). "Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function". Physiology & Behavior 92 (1–2): 210–7. :.  .
Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferré S (December 2007). . Progress in Neurobiology 83 (5): 277–92. :.  .  .
Cunha RA, Ferré S, Vaugeois JM, Chen JF (2008). . Current Pharmaceutical Design 14 (15): 1512–24. :.  .  .
Peart JN, Headrick JP (May 2007). "Adenosinergic cardioprotection: multiple receptors, multiple pathways". Pharmacology & Therapeutics 114 (2): 208–21. :.  .
Cohen MV, Downey JM (May 2008). "Adenosine: trigger and mediator of cardioprotection". Basic Research in Cardiology 103 (3): 203–15. :.  .
Ferré S (May 2008). "An update on the mechanisms of the psychostimulant effects of caffeine". Journal of Neurochemistry 105 (4): 1067–79. :.  .
Osadchii OE (June 2007). "Myocardial phosphodiesterases and regulation of cardiac contractility in health and cardiac disease". Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy 21 (3): 171–94. :.  .
Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility". Chemical Reviews 108 (1): 238–63. :.  .
Cristalli G, Lambertucci C, Marucci G, Volpini R, Dal Ben D (2008). "A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists". Current Pharmaceutical Design 14 (15): 1525–52. :.  .
Unless else specified in boxes, then ref is:
Jacobson KA, Gao ZG (2006). . Nature reviews. Drug discovery 5 (3): 247–64. :.  .  .
. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
at the US National Library of Medicine
: Hidden categories:From Wikipedia, the free encyclopedia
This article needs more
or relies too heavily on primary sources. Please review the contents of the article and
if you can. Unsourced or poorly sourced material may be . (January 2014)
Vinpocetine (brand names: Cavinton, Intelectol; chemical name: ethyl apovincaminate) is a
(sometimes described as "a
of "), an extract from the
plant. Vinpocetine was first isolated from the plant in 1975 by the Hungarian chemist Csaba Szántay. The mass production of the synthetic drug was started in 1978 by the Hungarian pharmaceutical company .
Vinpocetine is reported to have cerebral blood-flow enhancing and neuroprotective effects, and is used as a drug in Eastern Europe for the treatment of
and age-related memory impairment.
Vinpocetine is not approved in the United States for pharmaceutical use, but it can be sold as a dietary supplement. Vinpocetine is widely marketed as a supplement for
for the improvement of memory and cerebral metabolism. Vinpocetine has been identified as a potent anti-inflammatory agent that might have a potential role in the treatment of
As of 2003 only three controlled
had tested "older adults with memory problems". However, a 2003
determined that the results were inconclusive.
Prior to 2003, a different study from 1985 had tested young, healthy adults, but this study had 12 subjects and used a short treatment period.
Vinpocetine is widely used in the body building community as a . Although no studies have been conducted on the effectiveness of vinpocetine on performance enhancement during exercise, both beneficial and adverse effects have been reported on body building forums.[]
in rats has shown Vinpocetine to exhibit anticonvulsant properties, the most pronounced anticonvulsant effects were observed in
(PTZ)-kindled rats although there was also an effect on amygdala-kindled and neocortically-kindled rats. Vinpocetine has also been shown to abolished [3H]Glu release after in vivo exposure to
(4-AP) which suggests an important mechanism for vinpocetine anticonvulsant potential.
Vinpocetine has been identified as a novel
agent. Vinpocetine inhibits the up-regulation of
in various cell tests.
also shows that it reduced the TNFα-induced expression of the
of proinflammatory molecules such as ,
(MCP-1), and
(VCAM-1). In mice, vinpocetine reduced
inoculation induced
infiltration into the lung. Neuroinflammatory processes can result in neuronal death in
(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
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. 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.
Vinpocetine is also a
(PDE) type-1 inhibitor, (with an
of approximately 10-5 M.) leading to increases in intracellular levels of cyclic guanosine 3'5'-monophosphate (cGMP), an action that causes the vasorelaxant effects of vinpocetine on cerebral smooth muscle tissue.
Independent of vinpocetine's action on PDE, vinpocetine inhibits
preventing
degradation and the following translocation of
to the cell nucleus.
Increases in neuronal levels of , a metabolic breakdown product of , have been shown to occur in striatal isolated nerve endings as a result of exposure to vinpocetine. Such an effect is consistent with the biogenic pharmacology of , a structural relative of vinpocetine, which depletes catecholamine levels and causes
as a side effect of the cardiovascular and anti-psychotic effects. However, this effect tends to be reversible upon cessation of Vinpocetine administration, with full remission typically occurring within 3–4 weeks.
Vinpocetine is generally well-tolerated in humans. No serious side effects have thus far been noted in clinical trials, although none of these trials were long-term. Some users have reported headaches, especially at doses above 15 milligrams per day, as well as occasional upset stomach. Adverse drug-herb interactions have not been prevalent, and vinpocetine appears safe to take with other medications, including diabetes drugs, as well as blood thinners like . However, it should be carefully noted that the safety of vinpocetine in pregnant women has not been evaluated. Vinpocetine has been implicated in one case to induce , a condition in which
are markedly decreased. Some people have anecdotally noted that their continued use of vinpocetine reduces immune function.
warned that vinpocetine reduced immune function and could cause
(cellular death) in the long term.
L?rincz C, Szász K, Kisfaludy L (1976). "The synthesis of ethyl apovincaminate". Arzneimittel-Forschung 26 (10a): 1907.  .
Szilágyi, G. Z.; Nagy, Z. N.; Balkay, L. S.; Boros, I. N.; Emri, M. S.; Lehel, S.; Márián, T. Z.; Molnár, T. S.; Szakáll, S.; Trón, L.; Bereczki, D. N.; Csiba, L. S.; Fekete, I. N.; Kerényi, L.; Galuska, L. S.; Varga, J. Z.; B?n?czk, P. T.; Vas, ?. M.; Gulyás, B. Z. (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: 275–284. :.  . 
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". Acta pharmaceutica Hungarica 72 (2): 84–91.  . 
. Alternative Medicine Review 7 (3): 240–3. 2002.  .
Jeon, K. -I.; Xu, X.; Aizawa, T.; Lim, J. H.; Jono, H.; Kwon, D. -S.; Abe, J. -I.; Berk, B. C.; Li, J. -D.; Yan, C. (2010). . Proceedings of the National Academy of Sciences 107 (21): . :.  .  . 
Medina, A. E. (2010). . Proceedings of the National Academy of Sciences 107 (22): . :.  .  . 
McDaniel MA, Maier SF, Einstein GO (2003). "'Brain-specific' nutrients: a memory cure?". Nutrition 19 (11–12): 957–75. :.  .
Szatmari SZ, Whitehouse PJ (2003). Szatmári, Szabolcs, ed. "Vinpocetine for cognitive impairment and dementia". Cochrane Database of Systematic Reviews (1): CD003119. :.  .
Subhan Z, Hindmarch I (1985). "Psychopharmacological effects of vinpocetine in normal healthy volunteers". European Journal of Clinical Pharmacology 28 (5): 567–71. :.  .
Schmidt, J (1990). "Comparative studies on the anticonvulsant effectiveness of nootropic drugs in kindled rats". Biomedica biochimica acta 49 (5): 413–9.  .
Sitges, M; Sanchez-Tafolla, BM; Chiu, LM; Aldana, BI; Guarneros, A (2011). "Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs". Epilepsy research 96 (3): 257–66. :.  .
Sitges M, Galván E, Nekrassov V (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. :.  .
Adám-Vizi V (2000). "[Neuroprotective effect of sodium channel blockers in ischemia: the pathomechanism of early ischemic dysfunction]". Orvosi Hetilap (in Hungarian) 141 (23): 1279–86.  .
Hagiwara M, Endo T, Hidaka H (1984). "Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle".
33 (3): 453–7. :.  .
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. :.  .
Gurkovskaia AV, Gokina NI, Bury? VA, Shuba MF (1987). "[Electrophysiological analysis of the action of kavinton on the smooth muscles]". Biulleten' Eksperimental'no? Biologii I Meditsiny (in Russian) 103 (1): 68–71.  .
Trejo F, Nekrassov V, Sitges M (2001). "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings". Brain Research 909 (1–2): 59–67. :.  .
. foundhealth.
Shimizu Y, Saitoh K, Nakayama M, et al. . Medicine Online, Retrieved March 08, 2008.
The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines, 1st ed. 1998, Integrative Medicine Communications, Bk&CD-Rom edition, 1999.[]
: Hidden categories:Book types
Related topics
Early career researchers
Authors’ Update
Reviewers' Update
Industries
Special offers
Journal of the Neurological Sciences
Official Journal of the
provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world.
JNS places special emphasis on articles that: 1) provide guidance to clinicians around the world (Best Practices, Global Neurology); 2) report cutting-edge science related to neurology (Basic and Translational Sciences); 3) educate readers about relevant and practical clinical outcomes in neurology (Outcomes Research); and 4) summarize or editorialize the current state of the literature (Reviews, Commentaries, and Editorials).JNS accepts most types of manuscripts for consideration including original research papers, short communications, reviews, book reviews, letters to the Editor, opinions and editorials.
Topics considered will be from neurology-related fields that are of interest to practicing physicians around the world.
Examples include neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, epilepsies, disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.The fields covered may include neuroanatomy, neurochemistry, neuroendocrinology, neuroepidemiology, neurogenetics, neuroimmunology, neuroophthalmology, neuropathology, neuropharmacology, neurophysiology, neuropsychology, neuroradiology, neurosurgery, neurooncology, neurotoxicology, restorative neurology, and tropical neurology.The Journal of the Neurological Sciences is the official Journal of the World Federation of Neurology .
provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world.
JNS places special emphasis on articles...
Editor in Chief: Prof. John D. England, Richard M. Paddison Professor and Head
UsernamePassword
Source Normalized Impact per Paper (SNIP): 0.989Source Normalized Impact per Paper (SNIP):SNIP measures contextual citation impact by weighting citations based on the total number of citations in a subject field.SCImago Journal Rank (SJR): 1.079SCImago Journal Rank (SJR):SJR is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the G it provides a quantitative and a qualitative measure of the journal’s impact.Impact Factor: 2.262Impact Factor:The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years.(C) Thomson Reuters Journal Citation Reports 20145-Year Impact Factor: 2.379Five-Year Impact Factor:To calculate the five year Impact Factor, citations are counted in 2013 to the previous five years and divided by the source items published in the previous five years.(C) Journal Citation Reports 2014, Published by Thomson ReutersImprint: ELSEVIERISSN: X
Register your interests and receive email alerts tailored to your needs
Deb A. Kegelmeyer | Anne D. Kloos | ... Carolina Maruta | Sonya Makhmood | ... Virgilio Gerald H. Evidente | Daniel Truong | ...
Eun-Joo Kim | Jin-Hong Shin | ... Raita Fukasawa | Haruo Hanyu | ... Wataru Shiraishi | Shintaro Hayashi | ...
Volume 333, Issues 1-2 (2013)Volume 333, Supplement 1 (2013)Volume 322, Issues 1-2 (2012)
Paolo Zamboni | Erica Menegatti | ... Dag Aarsland | Martin Wilhelm Kurz
Chizobam O. Ani | Bruce Ovbiagele
Antonio Federico | Elena Cardaioli | ... Rima El-Abassi | Divya Singhal | ... Inan Olmez | Harold Moses | ...
Email a Friend
Complete the short form below to let your friends and colleagues know about this page.
Don't worry, the details you provide on this page will not be used to send unsolicited e-mail. Find out more about our .
Your Email
Friend's Name
Friend's Email
Thank you for recommending this page to a friend or colleague.}