Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.

Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.

Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

Comparison of the anti-inflammatory, analgesic and gastric effects of vinpocetine and piracetam in rats

The nootropic agents vinpocetine and piracetam are widely used in the treatment of memory and neurodegenerative disorders. The current study compared the effects of the two drugs in experimental models of inflammation and on the development of gastric mucosal damage evoked by indomethacin in rats. In paw oedema caused by subplantar injection of carrageenan, vinpocetine, given s.c., at doses of 0.45-1.8 mg/kg, produced only a slight decrease in paw volume. By contrast, piracetam administered s.c., at 75 mg/kg, significantly inhibited the oedema response, but at a higher dose 300 mg/kg produced a sustained dose-related increases in paw volume. In the hot-plate test of thermal pain, vinpocetine, but not piracetam, produced a dose-related reduction in nociceptive responses. Gastric mucosal lesions induced by s.c. indomethacin [20 mg/kg] were inhibited by vinpocetine [0.45-1.8 mg/kg, s.c.], but increased after piracetam [75-300 mg/kg, s.c.] in a dose-dependent manner. It is concluded that the nootropic drugs exert different effects on inflammation and gastric mucosal integrity in rats

Latency of memory consolidation induced in mice by piracetam, a nootropic agent.

Piracetam (PIR), a cyclic GABA derivative, is the prototype of a new class of psychoactive drugs, the nootropic agents, which improve learning acquisition and the retention of the learning as memory. It was proposed that nootropics act on processes essentially involved in information storage, thus facilitating memory. This property can best be investigated by drug administration after the learning trial and assessing subsequent retention performance. The present study was designed to evaluate the effective time period of memory consolidation, induced by piracetam, by assessing the retention of a learned task in two behavioural paradigms, following administration of the drug after learning acquisition. Physostigmine was used as the standard drug because of its well established facilitation of memory storage. PIR (250 and 500 mg/kg, ip) and physostigmine (0.05 mg/kg, ip) were administered in different groups of mice 5 min, 1, 2, 4, 8, 12 and 24 hr after learning acquistion of two passive avoidance tasks and the retention performance was evaluated 3 days later. The results indicate that, while physostigmine induced significant memory consolidation when administered up to 2 hr after learning acquisition, PIR induced retention of learning beyond this period. Thus, the highest effective post-trial interval for the lower and higher dose of the drug was 8 and 12 hr, respectively, in both the test paradigms. The results confirm that nootropics, like piracetam, are capable of memory consolidation, as assessed by retention of learning, even after intervals of 8 to 12 hr between learning and drug treatment.

Effect of piracetam on electroshock induced amnesia and decrease in brain acetylcholine in rats.

Piracetam, a prototype of a new class of psychotropic agents, the nootropic agents, which improve learning ability and memory retention, was found to induce a dose-related prevention of disruption of acquisition of a passive avoidance response produced by electroshock application. The amnesia attenuating effect of piracetam was accompanied by prevention of the decrease in acetylcholine concentrations of rat brain induced by electroshock. The study indicates that the cognition enhancing effect of piracetam may be due to a facilitatory effect on cholinergic transmission.

Dopaminergic involvement in the effects of piracetam on foot shock induced aggression in mice.

The effects of piracetam-a nootropic drug, were studied on foot shock induced aggressive behaviour in mice. Intraperitoneal injection of piracetam resulted in a biphasic response i.e.; initial excitation followed by inhibition of the aggressive behaviour. The initial excitation was observed with only 100 and 50 mg/kg doses of piracetam and not with the lower doses (25 and 12.5 mg/kg). Dopaminergic receptor blocker haloperidol (0.5; 0.25 and 0.12 mg/kg, ip) and pimozide (1.0 mg/kg, ip) produced inhibition of the aggressive behaviour. Lowering of the dose of haloperidol to 0.06 mg/kg resulted in an excitation of the aggressive behaviour. No motor deficit or catalepsy was observed with either haloperidol or pimozide injected in the doses indicated above. Pretreatment of the mice with haloperidol (0.12; 0.25 and 0.5 mg/kg) led to a dose-dependent blockade of the piracetam (100 mg) induced excitation of the aggressive behaviour, but the inhibition of the aggressive behaviour was not blocked by pretreatment with the excitatory dose of haloperidol. Similarly, pimozide (1.0 mg/kg) pretreatment also effectively blocked the excitatory effect of piracetam on aggressive behaviour. The results suggest the involvement of dopaminergic system in the excitatory effects of piracetam on aggressive behaviour. The inhibitory effect of piracetam appears to be independent of this mechanism.

Effect of piracetam, a nootropic agent, on discrimination learning deficits induced by parental undernutrition and environmental impoverishment in young rats.

The study was conducted on 64 Charles Foster albino rats which were equally distributed into 8 even-matched groups, following a 2 x 2 x 2 factorial design by varying three independent factors at two levels: nutrition--normal and undernutrition, environmental--enrichment and impoverishment, and drug treatment--vehicle and piracetam (100 mg/kg, ip). Prenatal nutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/drug treatments were given during the postweaning period of the rat pups. The animals were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. The results indicate that undernutrition and environmental impoverishment significantly attenuated the original discrimination as well as the reversal discrimination learning. Piracetam treatment improved the learning performance of normally reared rats and also attenuated the original and reversal learning deficits induced by prenatal undernutrition and postnatal impoverishment. The results indicate that piracetam may be useful in memory deficits induced by malnutrition.

Estudo das alteraçöes vasculares cerebrais com radioisótopos em portadores de aterosclerose cerebral e/ou seqüelas de acidente vascular cerebral, antes e após o uso da associaçäo piracetam-diidroergotoxina / Study of cerebral vascular diseases with radioisotopes in cerebral atherosclerotical subjects and/or subjects with sequelae of cerebral stroke, before and after the use of the association piracetam-dihydroergotoxine

Estudou-se o fluxo cerebral hemisférico completo e a cintigrafia cerebral em vinte (20) indivíduos, antes e após o uso da associaçäo piracetam com diidroergotoxina. Os indivíduos tratados eram portadores de aterosclerose cerebral e/ou de seqüelas estabilizadas de acidentes vasculares cerebrais. As cintigrafias cerebrais näo mostraram acúmulos anômalos do traçador radioativo em nenhuma ocasiäo. As velocidades circulatórias de ambos os hemisférios cerebrais diminuíram significativamente, provavelmente em razäo dos efeitos metabólicos cerebrais de ambos os fármacos, como também pela açäo simpaticolítica alfa e moduladora da circulaçäo cerebral proporcionada pela diidroergotoxina

Tratamiento del síndrome subjetivo post-traumático con Piracetam / The subjetive postcranial trauma syndrome treatment with piracetam

Se presenta un ensayo clínico realizado en 50 pacientes adultos, ambulatorios, quienes fueron diagnosticados como portadores del síndrome subjetivo post-traumático. Cada paciente fue examinado y controlado durante dos meses. De acuerdo con el procedimiento aceptado en los estudios `doble ciego' los pacientes fueron distribuídos al azar en dos grupos de 25, recibiendo uno de ellos, por vía oral, 4.8 gramos de piracetam y el otro tabletas de un placebo preparadas con la misma apariencia del producto activo. No fueron administrados otro medicamentos durante el período de observación. De los síntomas del síndrome subjetivo post-traumático, solamente 5 fueron encontrados con suficiente frecuencia para ser analizados estadísticamente: cefalea 49/50, fallas en la memoria 48/50, vértigo 39/50, insomnio 23/50 y trastornos auditivos 22/50. Los resultados son estadísticamente favorables al piracetam. La ventaja se observa desde la primera semana pero su mayor significación se alcanza después de la segunda semana y se mantiene hasta el final del estudio.

Effect of piracetam, a cyclic GABA analogue, on haloperidol-induced catalepsy in the rat.

Piracetam, 2-oxo-1-pyrrolidine acetamide (Nootropil), is a cyclic GABA analogue. As GABA-mimetic compounds have been reported to potentiate haloperidol-induced catalepsy it was decided to study the effect of piracetam on haloperidol-induced catalepsy in rats. Piracetam, in high doses, was found to induce catalepsy while sub-cataleptic doses of piracetam were found to potentiate haloperidol-induced catalepsy. Piracetam, however, failed to antagonise apomorphine stereotypy in rats thereby ruling out the possibility of its possessing dopamine receptor blocking activity. The possible mechanism involved in the induction of catalepsy by piracetam and in the potentiation of haloperidol-induced catalepsy by sub-cataleptic doses of piracetam is discussed on the basis of its chemical relationship to GABA.