Vinpotropile scientific update |
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Nomura T, Nishizaki T.
Department of Physiology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.
Nefiracetam facilitates hippocampal neurotransmission by a mechanism independent of the piracetam and aniracetam action.
A report on a mechanism independent of the piracetam and aniracetam action in which nefiracetam facilitates hippocampal neurotransmission. Nicotinic ACh receptor antagonists inhibit this facilitation. Facilitation of hippocampal neurotransmission is done by functionally targeting nicotinic ACh receptors.
Nefiracetam, a nootropic (cognition-enhancing) agent, facilitated neurotransmission in the dentate gyrus of rat hippocampal slices in a dose-dependent manner at concentrations ranged from 1 nM to 1 microM, being evident at 60-min washing-out of the drug. The facilitatory action was blocked by the nicotinic acetylcholine (ACh) receptor antagonists, alpha-bungarotoxin and mecamylamine. A similar facilitation was induced by the other nootropic agents, piracetam and aniracetam, but the facilitation was not inhibited by nicotinic ACh receptor antagonists and it did not occlude the potentiation induced by nefiracetam. In the Xenopus oocyte expression systems, nefiracetam potentiated currents through a variety of neuronal nicotinic ACh receptors (alpha 3beta 2, alpha 3beta 4, alpha 4 beta 2, alpha 4 beta 4, and alpha 7) to a different extent. In contrast, neither piracetam nor aniracetam had any potentiating action on alpha 7 receptor currents. While aniracetam delayed the decay time of currents through the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, GluR1, -2, -3, expressed in oocytes, nefiracetam or piracetam had no effect on the currents. Nefiracetam, thus, appears to facilitate hippocampal neurotransmission by functionally targeting nicotinic ACh receptors, independently of the action of piracetam and aniracetam.
CPD, Volume 8, Number 2, 1 January 2002, pp. 125-138(14)
Gualtieri, F.; Manetti, D.; Romanelli, M.; Ghelardini, C.
Design and Study of Piracetam-like Nootropics, Controversial Members of the Problematic Class of Cognition-Enhancing Drugs
An evaluation on the Piracetam-like Nootropics which is considered as the controversial members of the problematic class of cognition-enhancing drugs. This drug is capable to facilitate attentional abilities and acquisition. Cognition enhancers have never reached general acceptance yet.
Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes.
Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.
Usp Fiziol Nauk. 2003 Oct-Dec;34(4):16-25.
Solntseva EI, Bukanova IuV, Skrebitskii VG.
Brain Research Institute, Russian Academy of Medical Sciences, Moscow.
Memory and potassium channels
A report of a recent study on memory and potassium channels. Potassium channels inhibit neuronal excitement and cause neurodegeneration. This K(+) channels have connection with the mechanisms of memory disturbances.
The K(+)-channels of the surface membrane play a crucial role in the generation of electrical activity of a neuron. There is a large diversity of the K(+)-channels that depends on a great number (over 200) of genes encoding channels proteins. An evolutionary conservation of channel's proteins is determined. The K(+)-channels were found to have a great importance in the memory processes. It was shown on different model systems that K(+)-current of the surface membrane decreases during the learning. The antagonists of K(+)-channels were found to improve the learning and memory. It was revealed in electrophysiological experiments that K(+)-channels antagonists can either themselves induce a long-term synaptic potentiation or intensify the synaptic potentiation induced by a tetanization. The disfunction of K(+)-channels is believed to be an important link in the mechanisms of memory disturbances. In animal mutants with K(+)-channels disfunction, learning and memory are deficient. In behavioral experiments, the use of K(+)-channels openers make the learning worse. Amnesia caused by cerebral ischemia is explained by strong activity of K(+)-channels which not only inhibits neuronal excitement but also causes neurodegeneration. The question on the K(+)-channels involvement into pathophysiology of Alzheimer's disease is discussed. Neurotoxic peptide beta-amyloid, which is supposed to be involved into mechanisms of Alzheimer's disease, modulates K(+)-channels function. The effect of beta-amyloid depends on the subtype of K(+)-channels: A-channels are inhibited, and KDR-channels, on the contrary, become stronger. The effect of the cognitive enhancers (vinpocetine, piracetam, tacrine, linopirdine) on K(+)-current also depends on the subtype of K(+)-channels. Slow-inactivating K(+)-currents (IDR, IK(Ca), IM) are inhibited in the presence of these drugs, while fast-in-activating K(+)-current (A-current) remains unchanged or even increases.
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Drug category:Nootropic and smart drugs
 Vinpotropile scientific update
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