Disease relevance of Hydroxypiracetam

• The effects of oxiracetam on the reduction of brain metabolism induced by focal cerebral ischemia were investigated by measuring local cerebral glucose utilization (LCGU) in rats 24 hr after left middle cerebral artery occlusion [1].
• These findings suggest that oxiracetam minimizes the reduction of brain function induced by ischemia and may therefore be useful in the treatment of cerebrovascular disease [1].
• Evaluation of the detailed psychopathology by means of the Sandoz clinical assessment geriatric scale (SCAG) showed in the oxiracetam group significant improvements in loss of appetite and vertigo after 1 week and in short-term memory, anxiety, emotional lability, fatigue, loss of appetite and vertigo after 4 weeks [2].
• Treatment with oxiracetam (400 mg/kg/d p.o.) for 14 days after the occlusion showed a tendency to an improvement in the disturbed circadian rhythm but did not influence the size of brain infarction [3].

Psychiatry related information on Hydroxypiracetam

• Twenty-four carefully assessed patients with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled treatment study of oxiracetam, a nootropic agent reported to improve memory performance in patients with dementia [4].
• Treatment trial of oxiracetam in Alzheimer's disease [4].
• Effects of acute doses of oxiracetam in the scopolamine model of human amnesia [5].
• Pre- and postprandial pyridostigmine and oxiracetam effects on growth hormone secretion in anorexia nervosa [6].
• When compared with controls, C57 and DBA oxiracetam-treated mice showed no difference in motor skill capability to perform these complex learning tasks (swim speed or ability to freeze) [7].

High impact information on Hydroxypiracetam

• Indeed, oxiracetam crosses the blood-brain barrier and persists for longer in the CNS than in the serum [8].
• Oxiracetam, a nootropic drug, could be of potential use in the treatment of memory disturbances in patients with epilepsy who are using antiepileptic drugs [9].
• The half-life of oxiracetam appears to be influenced by the concomitant use of carbamazepine or valproic acid, necessitating more frequent administration of oxiracetam than is recommended for other conditions [9].
• The efficacy of an acute dose of oxiracetam in reducing scopolamine-induced cognitive impairment supports the potential usefulness of this pharmacological model of amnesia for studying the effects of cognition enhancers in humans [5].
• By contrast, oxiracetam attenuated the effect of scopolamine in the hippocampus, frontal cortex and striatum but not in the amygdala [10].

Chemical compound and disease context of Hydroxypiracetam

• Selegiline versus oxiracetam in patients with Alzheimer-type dementia [11].
• Oxiracetam prevents electroshock-induced decrease in brain acetylcholine and amnesia [12].
• These results show that oxiracetam prevents the imbalance of cholinergic activity and the amnesia caused by blockade of NMDA receptors [13].
• 1. Initial clinical trials in approximately 200 patients with dementias of diverse etiology suggested that oxiracetam, a structural analogue of the nootropic piracetam, was of some benefit in the treatment of cognitive dysfunction [14].
• In conclusion, these data demonstrate that ascorbic acid, alone or in combination with oxiracetam, may prevent experimentally induced amnesia in aged mice [15].

Biological context of Hydroxypiracetam

• 2. Superfusion of oxiracetam (0.1-100 microM) produced a concentration-dependent, wash-resistant (greater than 90 min), increase in initial slope and amplitude of the dendritic field excitatory postsynaptic potential (e.p.s.p.). This increase was maximal at a concentration of 1 microM (70%) [16].
• 4. Two trains of high frequency stimulation (100 Hz, 0.4 s, 5 min apart) delivered in the stratum radiatum 30 min after washout of oxiracetam (1 microM) still elicited a long-term potentiation (LTP) of the field e.p.s.p. However, the absolute magnitude of the LTP produced did not differ from that obtained in untreated slices [16].
• 14C oxiracetam administered directly into the lateral ventricles of the brain presented a similar pattern of distribution, indicating that the tropism of the drug for the above brain areas does not depend on its route of administration [17].
• Oxiracetam (100 mg/kg), a nootropic drug, did not affect the distribution of [3H]HCh-3 binding sites in sham-operated rats but completely overcame the reduction in the number of [3H]HCh-3 binding sites in deafferented striatum [18].
• The aim of this work was to study the effects of the nootropic drug oxiracetam, on lipid metabolism in rat brain [19].

Anatomical context of Hydroxypiracetam

• The oxiracetam effects present in slices could not be observed in hippocampal synaptosomes [20].
• Oxiracetam was administered intraperitoneally for 3 days prior to middle cerebral artery occlusion [1].
• Whereas oxiracetam elicited a moderate depressant effect on pyramidal cell excitability, piracetam increased it in a reversible fashion [21].
• Analysis of [3H]oxiracetam bound to membranes indicated that, after co-injection with a 1000-fold excess of unlabelled oxiracetam, there was a significant reduction of binding only in the septum, hippocampus and cerebral cortex [22].
• These results provide the first evidence in humans that oxiracetam penetrates the central nervous system and contribute to the understanding of its long-lasting pharmacodynamic effect in man [23].

Associations of Hydroxypiracetam with other chemical compounds

• Independent administration of DM-9384 (1, 3, 10 or 30 mg/kg, PO) or oxiracetam (10 or 50 mg/kg, PO) to mice had no effect on the ACh level in the hippocampus, frontal cortex, amygdala and striatum [10].
• The efficacy and tolerability of the monoamine oxidase B inhibitor selegiline and of the nootropic agent oxiracetam were compared in a single-blind, controlled, parallel study [11].
• The effects of different doses of scopolamine, and of the nootropic drugs oxiracetam and aniracetam, were investigated on the performance of male Wistar rats in a T-maze requiring a spatial discrimination in the stem (reference memory) and an alternate discrimination in the arms (working memory) [24].
• Oral administration of all of these drugs (BMY-21502, 3-300 mg/kg; Oxiracetam, 100-1000 mg/kg; Idebenone, 100-1000 mg/kg) failed to increase the number of gasps and the duration of gasping in the decapitated head of mice as a complete ischemic model [25].
• Choline incorporation into phospholipids in brain areas from spontaneously hypertensive rats: effect of oxiracetam treatment [26].

Gene context of Hydroxypiracetam

• Scopolamine also prevented the increase of particulate PKC elicited by oxiracetam in vitro [27].
• Oxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7 [13].
• The GABAB receptor antagonist CGP 36,742 and the nootropic oxiracetam facilitate the formation of long-term memory [28].
• At the end of therapy, statistical analysis (ANOVA) detected significant differences between groups: after oxiracetam treatment, improvements were observed on Mini Mental State Examination, Auditory Continuous Performance Test, Block Tapping Test, Word Fluency and Instrumental Activities of Daily Living. No side effects were observed [29].
• The effect was also observed in vitro when either oxiracetam or alpha GPC were administered at nanomolar concentrations to rat brain cortex slices [27].

Analytical, diagnostic and therapeutic context of Hydroxypiracetam

• Determination of oxiracetam in human plasma by reversed-phase high-performance liquid chromatography with fluorimetric detection [30].
• Reversed-phase HPLC methodology utilizing pre-column derivatization and post-column reaction fluorimetric detection has been developed and applied to the determination of oxiracetam in human plasma [30].
• EEG changes induced by oxiracetam on diazepam-medicated volunteers [31].
• At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole [32].
• In a 12-week double-blind study, oxiracetam (CGP 21690 E), a new nootropic drug, at a dose of 2.4 mg per day, was compared to placebo in the treatment of 106 middle-aged patients suffering from mild to moderate organic brain syndrome due to prolonged exposure to organic solvents [33].

References