LongeCity . Advocacy & Research for Unlimited Lifespans
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Posted 27 January 2005 - 04:46 PM
Posted by: nootropi Jan 19 2005, 12:38 PM
Arch Gerontol Geriatr. 1994 Mar-Apr;18(2):133-9.
Pramiracetam effects on scopolamine-induced amnesia in healthy volunteers.
Mauri M, Sinforiani E, Reverberi F, Merlo P, Bono G.
Dept. of Neurology, C. Mondino Foundation, University of Pavia, Pavia, Italy.
Pramiracetam has been evaluated for its potential antiamnesic properties in scopolamine-induced amnesia in healthy volunteers. Two groups of twelve males, 18-42 and 55-65 years old, respectively, were randomly assigned to oral treatment with pramiracetam (600 mg twice a day) or with placebo for 10 consecutive days. On day 11 each subject was injected intramascularly with scopolamine hydrobromide (0.5 mg). Before scopolamine injection and then 1, 3 and 6 h after it, subjects were administered the following psychometric tests: simple and choice visual reaction times, digit symbol substitution test, Rey's 15 words test for short and long term verbal memory. Scopolamine significantly impaired episodic memory and selective attention tests in both scopolamine and placebo groups. Instead visuo-motor and incidental learning measures were unaffected. Pramiracetam, when compared to placebo, was able to partially reduce the amnesic effects induced by scopolamine both in young and old subjects.
PMID: 15374306 [PubMed - in process]
So in this particular study, scopolamine was administered to several subjects, both young and old; and pramiracetam relieved the scopolamine-induced amnesia in healthy volunteers. Scopolamine is a drug that is commonly used in animal studies to impair the cholinergic system.
Posted by: nootropi Jan 19 2005, 12:39 PM
Lik Sprava. 2003 Dec;(8):67-72.
[Experience in the application of pramistar, a new nootropic preparation, in the treatment of memory disorders in patients with cerebrovascular pathology]
[Article in Russian]
Dziak LA, Golik VA, Miziakina EV.
Morbidity rise of cerebrovascular pathology is followed by remarkable cognitive decline. Chronic cerebral blood insufficiency and stroke consequences compose a group of the diseases which lead to different types of memory deterioration, consecutive memory decline and as a result to professional and social dysadaptation. The morphological basis of the problem consists in progressive structural cerebral deficit with forming a new adaptive system. The activity of this system is often not effective due to a lack of mediator supply. We have investigated the effects of monotherapy by a new nootropic drug--pramiracetam (Pramistar) on neuropsychological symptoms of memory deterioration in patients with chronic cerebrovascular insufficiency and stroke consequences in basilar and carotid vascular basin. The data obtained suggest statistically significant heterogeneous influence of the medicine on intensity of the evaluated symptoms.
PMID: 14965012 [PubMed - indexed for MEDLINE]
So this study shows that pramiracetam improves neuropsychological symptoms of memory deterioration in patients with chronic cerebrovascular insufficiency.
Posted by: nootropi Jan 19 2005, 12:41 PM
Hua Xi Yi Ke Da Xue Xue Bao. 1999 Dec;30(4):411-3.
[Pharmacokinetics of pramiracetam in animals]
[Article in Chinese]
Fang Z, Liu X, Xiao Y, Jiang W.
Department of Pharmacology, School of Basic Medical Sciences, WCUMS, Chengdu 610041.
Pharmacokinetic rules of pramiracetam were studied here. After giving pramiracetam orally to dogs, we drew their blood at various times. The drug concentrations in blood plasma were detected by HPLC. 3p87 program was used to calculate the pharmacokinetic parameters. The time-concentration curve corresponded to one apartment model. T1/2 was about 2.3-3.9 hours in various doses. After pramiracetam was given to rats per os, high concentrations of pramiracetam were detected in the rats' tissues. The kidney had the highest concentration of pramiracetam; the liver had the next highest concentration, and then the intestine, lung, muscle, heart, gonad, spleen and sebum had the high concentration in order. The drug was also detected in the brain. 0.7% of the given dose was excreted in unchanged form in bile in 24 hours. 28.26% and 6.35% were excreted in urine and feces respectively in 72 hours. The plasma protein combining rate detected by the method of balance dialysis was 20.1-22.2%.
PMID: 11387954 [PubMed - indexed for MEDLINE]
So this study tells us that, oddly, pramiracetam, when metabolised, is most highly concentrated in the DOG'S kidney. We surely then can expect similar results in humans.
Posted by: nootropi Jan 19 2005, 12:43 PM
Physiol Res. 1996;45(3):245-8.
The action of pramiracetam on consequences of hypobaric hypoxia is only moderate.
Maresova D, Mares P.
Institute of Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
The possible protective action of pramiracetam, a pyrrolidinone nootropic drug, against hypobaric hypoxia was studied in two age groups of immature rats with implanted electrodes. Epileptic afterdischarges induced by hippocampal stimulation were used as a measure of hypoxic damage. Pramiracetam did not substantially change these afterdischarges in 12- and 18-day-old rat pups which were not exposed to hypoxia. Hypobaric hypoxia (simulated altitude of 7000 m for one hour) led to prolongation of the first afterdischarge in both age groups. Pramiracetam did not influence this prolongation in 12-day-old rats. The first afterdischarge was shortened significantly in 18-day-old animals but not to the level of rats not exposed to hypoxia. The afterdischarges elicited by repeated stimulations (four times at 10 min intervals) did not differ in pramiracetam-treated and control rats.
PMID: 9200217 [PubMed - indexed for MEDLINE]
This study only thus tells us "The action of pramiracetam on consequences of hypobaric hypoxia is only moderate."
Posted by: nootropi Jan 19 2005, 12:46 PM
Funct Neurol. 1995 May-Jun;10(3):151-5.
Systemic administration of pramiracetam increases nitric oxide synthase activity in the cerebral cortex of the rat.
Corasaniti MT, Paoletti AM, Palma E, Granato T, Navarra M, Nistico G.
Faculty of Pharmacy, University of Reggio Calabria, Catanzaro, Italy.
The effect of systemic administration of pramiracetam on neuronal type nitric oxide synthase (NOS) activity and NOS mRNA expression were studied in the hippocampus and cerebral cortex in rats. A dose of 300 mg/kg (i.p.) of this nootropic produced an approximately 20% increase in NOS activity in rat brain cortical homogenates but not in hippocampal homogenates; no significant changes were observed in NOS mRNA expression in the cortex and hippocampus. A lower dose of pramiracetam (100 mg/kg i.p.) was ineffective on NOS mRNA expression and enzyme activity. Interestingly, administration of pramiracetam (300 mg/kg i.p.) in rats pretreated (24 h before) with lithium chloride (LiCl) (3 mEq/kg i.p.) yielded a 40% increase in cortical NOS activity. However, in LiCl-pretreated rats this nootropic failed to affect cortical NOS mRNA expression; LiCl (3 mEq/kg i.p.) given alone produced no effect. In conclusion, the present data demonstrate that pramiracetam given alone or in combination with LiCl increases NOS activity in brain cortical homogenates of rats and this may contribute to the mechanisms underlying learning and memory improvement produced by this nootropic.
PMID: 8557218 [PubMed - indexed for MEDLINE]
So this study infers that "pramiracetam given alone or in combination with LiCl increases NOS activity in brain cortical homogenates of rats and this may contribute to the mechanisms underlying learning and memory improvement produced by this nootropic."
Posted by: nootropi Jan 19 2005, 12:48 PM
Brain Res Brain Res Rev. 1994 May;19(2):180-222.
Piracetam and other structurally related nootropics.
Gouliaev AH, Senning A.
Department of Chemistry, Aarhus University, Denmark.
Nearly three decades have now passed since the discovery of the piracetam-like nootropics, compounds which exhibit cognition-enhancing properties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemical and behavioural results presented in the literature from 1965 through 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etiracetam, nefiracetam, aniracetam and rolziracetam and their structural analogues. The piracetam-like nootropics are capable of achieving reversal of amnesia induced by, e.g., scopolamine, electroconvulsive shock and hypoxia. Protection against barbiturate intoxication is observed and some benefit in clinical studies with patients suffering from mild to moderate degrees of dementia has been demonstrated. No affinity for the alpha 1-, alpha 2-, beta-, muscarinic, 5-hydroxytryptamine-, dopamine, adenosine-A1-, mu-opiate, gamma-aminobutyric acid (GABA) (except for nefiracetam (GABAA)), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack serious side effects. Increased turnover of different neurotransmitters has been observed as well as other biochemical findings, e.g., inhibition of enzymes such as prolylendopeptidase. So far, no generally accepted mechanism of action has, however, emerged. We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by, e.g., potentiated calcium influx through non-L-type voltage-dependent calcium channels, potentiated sodium influx through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible.
PMID: 8061686 [PubMed - indexed for MEDLINE]
This study reviews research on all piracetam-strcuturally related nootropics; and concludes:
"We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by, e.g., potentiated calcium influx through non-L-type voltage-dependent calcium channels, potentiated sodium influx through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible."
Posted by: nootropi Jan 19 2005, 12:50 PM
Int J Clin Pharmacol Res. 1992;12(3):129-32.
Pharmacokinetics of pramiracetam in healthy volunteers after oral administration.
Auteri A, Blardi P, Celasco G, Segre G, Urso R.
Institute of Clinical Medicine, University of Siena, Italy.
The pharmacokinetics of pramiracetam was assessed using an HPLC method after oral administration of two different formulations of 600 mg (a solution and a tablet) of pramiracetam to 11 fasting volunteers. The mean kinetic parameters were: t1 = 4.7 +/- 2.4 - 4.3 +/- 2.2 h, AUC = 57.6 +/- 43.6 - 47.2 +/- 33.9 micrograms h/ml, Cmax = 6.80 +/- 3.2 - 5.80 +/- 3.3 micrograms/ml for the solution and the tablet respectively. The plasma profile of pramiracetam proved to be not highly affected by the formulation, only that the absorption rate was faster after oral administration of the drug in solution than after administration as a tablet. The half-life was very variable between subjects [2-8 hours], but less variable within subjects and it was unaffected by the formulation.
PMID: 1473879 [PubMed - indexed for MEDLINE]
So this study concludes that the half life of pramiracetam is variable: "between 2 and 8 hours."
Posted by: nootropi Jan 19 2005, 12:52 PM
Psychopharmacology (Berl). 1992;108(1-2):11-5.
Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics.
Mondadori C, Ducret T, Hausler A.
Ciba-Geigy Ltd., Pharmaceutical Research Department, Basle, Switzerland.
Oral pretreatment of mice with aldosterone or corticosterone blocked the memory-enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose-related manner, without, however, impairing the animals' learning performance. The improvement of memory induced by physostigmine, arecoline, and tacrine (THA) was similarly inhibited. The fact that elevated steroid levels suppress the memory-enhancing effects of entirely different substances could indicate that these substances have a common site of action. In the light of new observations showing increased cortisol concentrations in Alzheimer patients, this steroid dependency of the effects of memory enhancers might explain why only a limited number of these patients respond to therapy with nootropics or cholinomimetics.
PMID: 1410129 [PubMed - indexed for MEDLINE]
So this study shows us that: "Oral pretreatment of mice with aldosterone or corticosterone blocked the memory-enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose-related manner, without, however, impairing the animals' learning performance."
Posted by: nootropi Jan 19 2005, 12:55 PM
Brain Inj. 1991 Oct-Dec;5(4):375-80.
Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia.
McLean A Jr, Cardenas DD, Burgess D, Gamzu E.
Neuro Care Inc., Seattle, Washington.
The current study evaluated under double-blind placebo-controlled conditions, the safety and efficacy of 400 mg pramiracetam sulphate TID in treating memory and other cognitive problems of males who have sustained brain injuries. The results of the study indicate that subject performance in measures of memory, especially delayed recall, evidenced clinically significant improvements after the administration of pramiracetam sulphate as compared to placebo. This improvement was maintained during an 18-month open-trial period on the medication as well as during a 1-month follow-up period after the pramiracetam was discontinued.
Randomized Controlled Trial
PMID: 1786500 [PubMed - indexed for MEDLINE]
So this study shows that 400 mg pramiracetam sulphate TID in AN 18 month controlled trial "evidenced clinically significant improvements after the administration of pramiracetam sulphate as compared to placebo."
Posted by: nootropi Jan 19 2005, 12:56 PM
Neurology. 1991 Apr;41(4):570-4.
Nootropic drugs in Alzheimer's disease: symptomatic treatment with pramiracetam.
Claus JJ, Ludwig C, Mohr E, Giuffra M, Blin J, Chase TN.
Experimental Therapeutics Branch, National Institutes of Neurological Disorders and Stroke, Bethesda, MD 20892.
The cognitive-enhancing effects of pramiracetam in animal models of learning and memory are characterized by an inverted U-shaped dose-response curve. We evaluated antidementia efficacy of this drug in 10 patients with probable Alzheimer's disease employing a 2-phase, placebo-controlled, enrichment-type trial design. Eight patients evidenced a best dose in the dose-finding phase, but in the subsequent replication phase only two again improved to a similar degree. PETs with fluorodeoxyglucose obtained in two individuals showed no definite change. Doses up to 4,000 mg pramiracetam are unlikely to confer symptomatic benefit to Alzheimer's disease patients.
Controlled Clinical Trial
PMID: 2011259 [PubMed - indexed for MEDLINE]
This study shows that Doses up to 4,000 mg pramiracetam are unlikely to confer symptomatic benefit to Alzheimer's disease patients.
Posted by: nootropi Jan 19 2005, 12:58 PM
Brain Res. 1990 Jan 1;506(1):101-8.
Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics.
Mondadori C, Bhatnagar A, Borkowski J, Hausler A.
Pharmaceutical Research Department, CIBA-GEIGY Limited, Basle, Switzerland.
Since adrenalectomy abolishes the memory-enhancing effects of piracetam and its derivatives, oxiracetam, aniracetam and pramiracetam, the question arises whether endogenous steroids play a role in their mechanism of action. We show that inhibition of steroid biosynthesis by aminoglutethimide and blockade of the aldosterone receptors by epoxymexrenone completely suppress the memory-improving effects of the nootropics. These results indicate that steroids, or, more precisely, activities mediated by the aldosterone receptors, might be involved in the mechanism of action of this class of nootropics. Blockade of aldosterone receptors, however, does not block the effects of cholinomimetics on memory, indicating the involvement of another mechanism of action.
PMID: 2137359 [PubMed - indexed for MEDLINE]
So this study shows that "steroids, or, more precisely, activities mediated by the aldosterone receptors, might be involved in the mechanism of action of this class of nootropics."
Posted by: nootropi Jan 19 2005, 12:59 PM
Arzneimittelforschung. 1989 Oct;39(10):1220-2.
Reversal of scopolamine-induced alterations of choline transport across the blood-brain barrier by the nootropics piracetam and pramiracetam.
Department of Cell Biology and Regulation, Karl Marx University, Leipzig, German Democratic Republic.
The choline transport across the blood-brain barrier was studied in nine brain regions of male Wistar rats after treatment with scopolamine, piracetam and pramiracetam, respectively. 14-Day treatment with scopolamine (0.5 mg/kg/d) elicited an increase of the extraction and the PS-product (permeability-surface area) of choline which was prevented by coinjection of piracetam or pramiracetam (100 mg/kg/d). In addition, the cerebral blood flow was increased by both nootropics. Differences between various brain regions were found in both choline transport and cerebral blood flow. It is supposed from the results that the choline transport is regulated by cholinergic innervation of the brain endothelial cells and that the nootropics used may act via alterations of the brain choline metabolism.
PMID: 2610714 [PubMed - indexed for MEDLINE]
This study shows that: "the results that the choline transport is regulated by cholinergic innervation of the brain endothelial cells and that the nootropics used may act via alterations of the brain choline metabolism."
Posted by: nootropi Jan 19 2005, 01:00 PM
Behav Brain Res. 1989 Jun 1;33(2):197-207.
A new one-trial test for neurobiological studies of memory in rats. II: Effects of piracetam and pramiracetam.
Ennaceur A, Cavoy A, Costa JC, Delacour J.
Laboratoire de Psychophysiologie, Universite Paris VII, France.
The effects of the nootropic drugs Piracetam (Pir) and Pramiracetam (Pram) were evaluated on recognition-memory of rats in a new one-trial test. This test is based on spontaneous exploratory activity and does not involve rule learning or reinforcement. Recognition is measured by the time spent by rats in exploring two different objects, one familiar (the sample), the other new. When the retention interval is 1 min, normal rats spend more time exploring the new object which demonstrates that they recognize the familiar one, but they do not discriminate between the two objects after a 24-h interval. Three doses of Pram (15, 30 and 60 mg/kg) and Pir (100, 200 and 400 mg/kg) were administered i.p. 30 min before the acquisition trial. The doses of 30 mg/kg of Pram and of 400 mg/kg of Pir produced a significant improvement in retention when the intertrial interval was 24 h. This effect was not associated with a change in overall exploratory behavior. This study shows that the new object-recognition test may be a useful tool for pharmacological studies of memory in rats.
PMID: 2765166 [PubMed - indexed for MEDLINE]
"This study shows that the new object-recognition test may be a useful tool for pharmacological studies of memory in rats."
Posted by: nootropi Jan 19 2005, 01:01 PM
Behav Brain Res. 1989 May 1;33(1):79-82.
The memory-enhancing effects of the piracetam-like nootropics are dependent on experimental parameters.
Mondadori C, Ducret T, Borkowski J.
Pharmaceutical Research Department, CIBA-GEIGY Limited, Basle, Switzerland.
The effects of the nootropic agent piracetam and its congeners oxiracetam, pramiracetam and aniracetam on the retention performance of mice in a passive-avoidance situation are dependent on the intensity of the foot-shock applied. This phenomenon is observed upon both pre-trial and post-trial drug administration.
PMID: 2736062 [PubMed - indexed for MEDLINE]
So "The effects of the nootropic agent piracetam and its congeners oxiracetam, pramiracetam and aniracetam on the retention performance of mice in a passive-avoidance situation are dependent on the intensity of the foot-shock applied."
Posted by: nootropi Jan 19 2005, 01:02 PM
Prog Neuropsychopharmacol Biol Psychiatry. 1989;13 Suppl:S77-88.
Nootropic drugs and brain cholinergic mechanisms.
Pepeu G, Spignoli G.
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
1. This review has two aims: first, to marshal and discuss evidences demonstrating an interaction between nootropic drugs and brain cholinergic mechanisms; second, to define the relationship between the effects on cholinergic mechanisms and the cognitive process. 2. Direct or indirect evidences indicating an activation of cholinergic mechanisms exist for pyrrolidinone derivatives including piracetam, oxiracetam, aniracetam, pyroglutamic acid, tenilsetam and pramiracetam and for miscellaneous chemical structures such as vinpocetine, naloxone, ebiratide and phosphatidylserine. All these drugs prevent or revert scopolamine-induced disruption of several learning and memory paradigms in animal and man. 3. Some of the pyrrolidinone derivatives also prevent amnesia associated with inhibition of acetylcholine synthesis brought about by hemicholinium. Oxiracetam prevents the decrease in brain acetylcholine and amnesia caused by electroconvulsive shock. Oxiracetam, aniracetam and pyroglutamic acid prevent brain acetylcholine decrease and amnesia induced by scopolamine. Comparable bell-shaped dose-effect relationships result for both actions. Phosphatidylserine restores acetylcholine synthesis and conditioned responses in aging rats. 4. The mechanisms through which the action on cholinergic systems might take place, including stimulation of the high affinity choline uptake, are discussed. The information available are not yet sufficient to define at which steps of the cognitive process the action on cholinergic system plays a role and which are the influences of the changes in cholinergic function on other neurochemical mechanisms of learning and memory.
PMID: 2694231 [PubMed - indexed for MEDLINE]
Posted by: nootropi Jan 19 2005, 01:03 PM
Biomed Biochim Acta. 1988;47(4-5):417-21.
[Cholinergic effects of nootropics]
[Article in German]
Funk KF, Schmidt J.
Institut fur Pharmakologie und Toxikologie, Medizinische Akademie Carl Gustav Carus, Dresden, DDR.
With respect to the enhancing effect of nootropics on learning and memory, the influence of some of these drugs on the high affinity choline uptake has been investigated. Meclofenoxate competes with choline uptake in vitro because of its similar side chain; other nootropics are without in vitro effects. A single dose of pramiracetam enhances the choline uptake in cortex and hippocampus. Application of meclofenoxate decreases the uptake of choline. Other nootropics lack acute effects. Possible increases of uptake after repeated dosage disappear within 24 h.
PMID: 3149192 [PubMed - indexed for MEDLINE]
So: "A single dose of pramiracetam enhances the choline uptake in cortex and hippocampus."
Posted by: nootropi Jan 19 2005, 01:06 PM
Act Nerv Super (Praha). 1987 Mar;29(1):62-5.
Effects of nootropic drugs on brain cholinergic and dopaminergic transmission.
Pavlik A, Benesova O, Dlohozkova N.
High affinity choline uptake (HACU) in the hippocampus and striatal concentration of dopamine (DA) and homovanillic acid (HVA) as measures of the in vivo acetylcholine and DA turnover, respectively, were estimated in male rats, Long-Evans, following 6-day administration of various nootropics in clinically relevant doses: piracetam and its derivatives pramiracetam and oxiracetam (100 mg/kg/day), pyritinol (50 mg/kg/day). Piracetam treatment was without effect on HACU, but induced significant increase of HVA in the striatum leaving striatal DA concentration unchanged. On the contrary, pyritinol, pramiracetam and oxiracetam increased HACU, but did not change striatal DA and HVA levels.
PMID: 3035858 [PubMed - indexed for MEDLINE]
"On the contrary, pyritinol, pramiracetam and oxiracetam increased HACU, but did not change striatal DA [Dopamine] and HVA[Homovanillic acid (HVA)] levels"
dopamine becomes HVA
norepinephrine becomes normetanephrine and VMA
epinephrine becomes metanephrine and VMA
Data source (Secondary) http://drkoop.com/en...icle/003613.htm
Posted by: nootropi Jan 19 2005, 01:06 PM
Pharmacol Biochem Behav. 1986 Oct;25(4):925-7.
Amnesia produced by intracerebroventricular injections of hemicholinium-3 in mice was prevented by pretreatment with piracetam-like compounds.
Franklin SR, Sethy VH, Tang AH.
Intracerebroventricular (ICV) injections of hemicholinium-3 (HC-3) to mice before the training trial in a passive avoidance task produced an amnesic effect at the 24-hour retention test. Pretreatment by IP injection of piracetam, etiracetam, or pramiracetam, 30 minutes before HC-3 injections antagonized the amnesic effects of HC-3. Pretreatment with choline was not effective. The depletion of cerebral acetylcholine by the HC-3 injection was not prevented by piracetam or etiracetam.
PMID: 3786350 [PubMed - indexed for MEDLINE]
So the effect of HC-3 is more powerful than the contrary effects of piracetam or etiracetam. This does not help us very much; that is, unless you plan on taking injections of HC-3.
Posted by: nootropi Jan 19 2005, 01:08 PM
Neuropharmacology. 1986 Oct;25(10):1161-6.
The effects of cholinergic drugs support an avoidance learning hypothesis of brief footshock-induced analgesia.
Gower AJ, Tricklebank MD.
Rats were tested for tail-flick responses and then immediately subjected to footshock for 30 sec. This procedure induced analgesia, i.e. prolonged the latency of the tail-flick response, which was maximal immediately after the shock and decayed to normal levels within 2 hr. No analgesia occurred if either the analgesia test before the shock or the shock itself was omitted. The dependence of the analgesia on the association between the test before the shock plus the shock, suggests that this was a form of avoidance learning. The effects of drugs injected immediately after the shock were determined on latency of the tail-flick response, measured 2 hr later. Drugs known to improve memory, including physostigmine, pramiracetam and the muscarinic agonists, oxotremorine and RS 86, selectively induced analgesia in rats subjected to test before the shock plus the shock, thereby supporting a hypothesis of avoidance learning. Neostigmine and atropine methyl nitrate had no effect, indicating that the effects were mediated centrally. The learning effects were distinguishable from analgesia induced by drugs, since morphine increased analgesia regardless of the presence or absence of the test before shock or the shock. Also, naloxone, which had no effect per se, blocked analgesia induced by morphine but enhanced physostigmine-induced analgesia. Neither chlordiazepoxide nor D-amphetamine produced any changes in the latency of the tail-flick responses indicating that neither anxiolytic/muscle relaxant nor stimulant actions were involved.
PMID: 3785583 [PubMed - indexed for MEDLINE]
Posted by: nootropi Jan 19 2005, 02:43 PM
Psychopharmacology (Berl). 1986;89(3):378-81.
The effect of pramiracetam (CI-879) on the acquisition of a radial arm maze task.
Murray CL, Fibiger HC.
The effect of the nootropic drug pramiracetam (CI-879) on acquisition of a radial arm maze task was examined in the rat. Two doses of pramiracetam (7.5 mg/kg and 15 mg/kg) were administered daily prior to testing for 7 weeks in a 16-arm radial maze in which nine arms were baited with food. This procedure permitted a distinction between working memory (short-term) and reference memory (long-term). Both doses of pramiracetam significantly improved performance in the reference memory component of the task, but did not significantly affect the working memory component. These data indicate that pramiracetam can enhance some aspects of spatial learning and memory in the rat.
PMID: 3088666 [PubMed - indexed for MEDLINE]
So "Both doses of pramiracetam significantly improved performance in the reference memory component of the task, but did not significantly affect the working memory component. These data indicate that pramiracetam can enhance some aspects of spatial learning and memory in the rat."
Posted by: nootropi Jan 19 2005, 02:46 PM
Experientia. 1985 Sep 15;41(9):1153-6.
Pharmacologic therapeutic window of pramiracetam demonstrated in behavior, EEG, and single neuron firing rates.
Poschel BP, Ho PM, Ninteman FW, Callahan MJ.
Following oral or intravenous administration, a representative cognition activator drug, pramiracetam sulfate, is shown to have a pharmacologic therapeutic window at three different levels of study: learned behavior, gross EEG activity of the frontal cortex and hippocampus, and firing rate of single hippocampal neurons.
PMID: 4043326 [PubMed - indexed for MEDLINE]
Posted by: nootropi Jan 19 2005, 02:48 PM
Life Sci. 1985 Jun 3;36(22):2145-52.
The effects of various cognition-enhancing drugs on in vitro rat hippocampal synaptosomal sodium dependent high affinity choline uptake.
Shih YH, Pugsley TA.
The purpose of the present study was to compare the effect of seven drugs, that have been reported to enhance cognitive functions, on rat hippocampal cholinergic neuronal activity. The latter was assessed by measuring the effects of the drugs on in vitro sodium-dependent high affinity choline uptake (HACU) into rat hippocampal synaptosomes 30 minutes after their in vivo administration. 3,4-Diaminopyridine (0.1 mg/kg IP), like pramiracetam (44 and 88 mg/kg IP), increased HACU with higher or lower doses being ineffective. Centrophenoxine (100 mg/kg IP) decreased HACU. Piracetam (100 and 500 mg/kg IP), aniracetam (10-200 mg/kg PO), lysine vasopressin (0.005-0.05 mg/kg IM) and 4-aminopyridine (0.01-3.0 mg/kg IP) were ineffective. The results indicate that 3,4-diaminopyridine and centrophenoxine, like pramiracetam may be increasing cognitive function in part by affecting hippocampal cholinergic neuronal activity. In addition, the findings indicate the usefulness of using in vitro HACU as a biochemical measurement to assess the potential effect of cognitive-enhancing drugs on cholinergic neuronal activity in vivo.PMID: 2987637 [PubMed - indexed for MEDLINE]
Posted by: nootropi Jan 19 2005, 02:52 PM
J Clin Pharmacol. 1985 May-Jun;25(4):291-5.
Pharmacokinetics of oral pramiracetam in normal volunteers.
Chang T, Young RM, Goulet JR, Yakatan GJ.
The pharmacokinetics of pramiracetam, a new, investigational, cognition activator, were assessed in normal male volunteers as part of a clinical tolerance study. In a double-blind, randomized design, two groups of six subjects each received alternating placebo and single 400, 800, 1,200, and 1,600 mg oral doses of pramiracetam after an overnight fast. Mean (+/- SD) peak plasma concentrations of the four dose groups (2.71 +/- 0.54, 5.40 +/- 1.34, 6.13 +/- 0.71, 8.98 +/- 0.71 micrograms/mL) were attained between two to three hours following drug administration. The harmonic mean elimination half-life (4.5-6.5 hours), the mean total body clearance (4.45-4.85 mL/min/kg), the mean renal clearance (1.83-3.00 mL/min/kg), and the mean apparent volume of distribution (1.82-2.94 L/kg) were independent of dose, whereas the peak plasma concentrations and area under the curves increased as a linear function of dose. No significant side effects were observed at any dose level.
Randomized Controlled Trial
PMID: 4008675 [PubMed - indexed for MEDLINE]
So this confirms pramiracetam's safety in normal subjects...and that: "The harmonic mean elimination half-life (4.5-6.5 hours), the mean total body clearance (4.45-4.85 mL/min/kg), the mean renal clearance (1.83-3.00 mL/min/kg), and the mean apparent volume of distribution (1.82-2.94 L/kg) were independent of dose, whereas the peak plasma concentrations and area under the curves increased as a linear function of dose. No significant side effects were observed at any dose level."
Posted by: nootropi Jan 19 2005, 02:55 PM
J Med Chem. 1984 May;27(5):684-91.
Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam.
Butler DE, Nordin IC, L'Italien YJ, Zweisler L, Poschel PH, Marriott JG.
A series of N-[(dialkylamino)alkyl]-2-oxo-1- pyrrolidineacetamides was synthesized. The title compounds reversed electroconvulsive shock (ECS) induced amnesia in mice when administered subsequent to the ECS treatment and were inactive in a general observational test for central nervous system (CNS) activity. Active compounds exhibited an inverted U-shaped dose-response curve. Among the compounds with the broadest dose-response curve, as well as the most potent, were those with the N-[2-[bis(1-methylethyl)amino] ethyl] or 2,6- dimethylpiperidinoethyl residues as amide substituent. The N-(dialkylamino) substituent markedly enhances amnesia-reversal activity, with ethylene providing the optimal chain length. N-[2-[Bis(1-methylethyl)amino]ethyl] -2-oxo-1- pyrrolidineacetamide N-(dialkylamino) substituent was selected for preclinical toxicological evaluation, assigned the investigational number CI-879 and the U.S. adopted name ( USAN ) pramiracetam . Pramiracetam demonstrated a wide margin of safety in animals and was well tolerated in normal human volunteers. It has shown encouraging activity in an open label trial in patients with primary degenerative dementia (PDD or senile dementia of the Alzheimer's type).
PMID: 6716406 [PubMed - indexed for MEDLINE]
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