2-오소-1-피리딘아세트아마이드;피라세탐

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

log Kow = -1.54

-1.54

136.8 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID5044491]

134.42 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

This chemical does not meet GHS hazard criteria for 92.1% (58 of 63) of all reports.

Not Classified

Aggregated GHS information provided per 63 reports by companies from 6 notifications to the ECHA C&L Inventory.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

... Confusion, irritability and sleep disorders /have been/ reported with concomitant use /of/ thyroid extract (T3 + T4) /and piracetam/.

At present although based on a small number of patients, no interaction has been found with the following anti-epileptic medications: clonazepam, carbamazepine, phenytoin, phenobarbitone and sodium valproate.

In a single-blind study on patients with severe recurrent venous thrombosis, piracetam 9.6 g/d did not modify the doses of acenocoumarol necessary to reach INR (international normalized ratio) 2.5 to 3.5, but compared with the effects of acenocoumarol alone, the addition of piracetam 9.6 g/d significantly decreased platelet aggregation, beta-thromboglobulin release, levels of fibrinogen and von Willebrand's factors (VIII : C; VIII : vW : Ag; VIII : vW : RCo) and whole blood and plasma viscosity.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Piracetam

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Acute toxicological studies in animals showed lethal doses were obtained in mice (18.2 g/kg and higher) but not in rats and dogs dosed respectively at 21 g/kg or 10 g/kg.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The only change which might eventually be attributed to chronic treatment in male, but not in female, rats was an increase of the incidence over control animals of progressive glomerulonephrosis at the dose of 2.4 g/kg/day given for 112 weeks.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Repeated oral treatment for up to 1 year in dogs (10 g/kg) and 6 months in rats (2 g/kg) was very well tolerated: no target organ toxicity or signs of (irreversible) toxicity were clearly demonstrated.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Although piracetam crosses the placenta into the fetal circulation, no teratogenic effects were observed at dose levels up to 4.8 g/kg/day (mice, rats) and 2.7 g/kg/day (rabbits). Furthermore, the compound affects neither fertility nor the peri- or postnatal development of the pregnancy at doses up to 2.7 g/kg/day.

/GENOTOXICITY/ Piracetam was found to be devoid of any mutagenic or clastogenic activity and does not represent any genotoxic ... risk to man.

While data specific to piracetam were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

N06BX03

N - Nervous system

QN - Nervous system

Piracetam is known to mediate various pharmacodynamic actions: **Neuronal effects**: Piracetam modulates the cholinergic, serotonergic, noradrenergic, and glutamatergic neurotransmission although the drug does not display high affinity to any of the associated receptors (Ki >10μM). Instead, piracetam increases the density of postsynaptic receptors and/or restore the function of these receptors through stabilizing the membrane fluidity. In the forebrain of aging mice, the density of NMDA receptors was increased by approximately 20% following 14 days of piracetam treatment. Based on the findings of various animal and human studies, the cognitive processses including learning, memory, attention and consciousness were enhanced from piracetam therapy without inducing sedation and psychostimulant effects. Piracetam mediate neuroprotective effects against hypoxia-induced damage, intoxication, and electroconvulsive therapy. In two studies involving alcohol-treated rats with evidences of withdrawal-related neuronal loss, piracetam was shown to reduce the extent of neuronal loss and increase the numbers of synapses in the hippocampus by up to 20% relative to alcohol-treated or alcohol-withdrawn rats. This suggests that piracetam is capable in promoting neuroplasticity when recoverable neural circuits are present. Although the mechanism of action is not fully understood, administration of piracetam prior to a convulsant stimulus reduces the seizure severity and enhances the anticonvulsant effectiveness of conventional antiepileptics such as carbamazepine and diazepam. **Vascular effects**: Piracetam is shown to increase the deformability of erythrocytes, reduce platelet aggregation in a dose-dependent manner, reduce the adhesion of erythrocytes to vascular endothelium and capillary vasospasm. In healthy volunteers, piracetam mediated a direct stimulant effect on prostacycline synthesis and reduced the plasma levels of fibrinogen and von Willebrand’s factors (VIII: C; VIII R: AG; VIII R: vW) by 30 to 40%. Potentiated microcirculation is thought to arise from a combination of effects on erythrocytes, blood vessels and blood coagulation.

Piracetam interacts with the polar heads in the phospholipids membrane and the resulting mobile drug-lipid complexes are thought to reorganize the lipids and influence membrane function and fluidity. Such interaction has been reported in a study that investigated the effects of neuronal outgrowth induced by beta amyloid peptides; while amyloid peptides cause lipid disorganization within the cell membranes leading to neuronal death, piracetam demonstrated to decrease the destabilizing effects of amyloid peptide. The authors suggest that piracetam induces a positive curvature of the membrane by occupying the polar groups in the phospholipids to counteract the negative curvature induced by amyloid peptides , which in turn would decrease the likelihood of membrane fusion. This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function such as membrane transport, chemical secretion, and receptor binding and stimulation. Through restored membrane fluidity, piracetam promotes restored neurotransmission such as glutamatergic and cholinergic systems, enhances neuroplasticity and mediates neuroprotective and anticonvulsant effects at the neuronal level. It is also demonstrated that piracetam also improves the fluidity of platelet membranes. At the vascular level, piracetam decreases adhesion of erythrocytes to cell wall and reduces vasospasm which in turn improves microcirculation including cerebral and renal blood flow.

It was found that a drug of the nootropic nature piracetam possessing pronounced antihypoxic properties eliminates calcium chloride-induced disturbances of the cardiac rhythm and significantly raises the threshold of atrial fibrillation during electrical stimulation. The drug's antiarrhythmic effect is followed by a decrease of the rhythm rate and an increase of the contraction amplitude. The animals treated with piracetam in a dose when its antiarrhythmic effects (300 mg/kg) exhibited a decrease of the membrane potential of erythrocytes as compared with control. Similar effects occurred in the animals treated with lidocaine. It can be concluded that in certain types of arrhythmias the use of piracetam restores the normal rhythm of contractions that is perhaps connected with its positive influence on metabolic processes in the myocardium.

The plasma half life of piracetam is approximately 5 hours following oral or intravenous administration. The half life in the cerebrospinal fluid was 8.5 hours.

... The plasma half-life is 5.0 hours, in young adult men.

As large proportion of total piracetam administered is excreted as unchanged drug, there is no known major metabolism of piracetam.

... No metabolite of piracetam has been found.

Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.

Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms.

Piracetam displays a linear and time-dependent pharmacokinetic properties with low intersubject variability over a large range of doses. Piracetam is rapidly and extensively absorbed following oral administration with the peak plasma concentration is reached within 1 hour after dosing in fasted subjects. Following a single oral dose of 3.2 g piracetam, the peak plasma concentration (Cmax) was 84 µg/mL. Intake of food may decrease the Cmax by 17% and increase the time to reach Cmax (Tmax) from 1 to 1.5 hours. Tmax in the cerebrospinal fluid is achieved approximately 5 hours post-administration. The absolute bioavailability of piracetam oral formulations is close to 100% and the steady state plasma concentrations are achieved within 3 days of dosing.

Piracetam is predominantly excreted via renal elimination, where about 80-100% of the total dose is recovered in the urine. Approximately 90% of the dose of piracetam is excreted in the urine as unchanged drug.

Vd is approximately 0.6L/kg. Piracetam may cross the blood-brain barrier as it was measured in the cerebrospinal fluid following intravenous administration. Piracetam diffuses to all tissues except adipose tissues, crosses placental barrier and penetrates the membranes of isolated red blood cells.

The apparent total body clearance is 80-90 mL/min.

Piracetam is rapidly and almost completely absorbed. Peak plasma levels are reached within 1.5 hours after administration. The extent of oral bioavailability, assessed from the Area Under Curve (AUC), is close to 100% for capsules, tablets and solution.

Peak levels and AUC are proportional to the dose given. The volume of distribution of piracetam is 0.7 L/kg, and ... Clearance of the compound is dependent on the renal creatinine clearance and would be expected to diminish with renal insufficiency.

Cerebral stimulant drug

MEDICATION

THERAP CAT: Nootropic

Use (kg; approx.) in Germany (2009): >50000

... Prepared by condensing 2-pyrrolidinone with ethyl chloroacetate in the presence of a metal hydride and then converting the ester into an amide with ammonia.

Prepn: H. Morren, NL 6509994; eidem, US 3459738 (1966, 1969 both to U.C.B)

Nootropil 800 and 1200 mg Tablets: Polyethylene glycol 6000, Colloidal anhydrous silica, Magnesium stearate, Methocel, Titanium dioxide (E171), Polyethylene glycol 400. Nootropil Solution 33%: Glycerol, Methyl parahydroxybenzoate, Propyl parahydroxybenzoate, Sodium acetate, Acetic acid, Purified water

Avigilen

Axonyl

Ciclofalina

For more Formulations/Preparations (Complete) data for PIRACETAM (19 total), please visit the HSDB record page.

January 7, 1999. ... /Piracetam is not/ the subject of a current United States Pharmacopeia or National Formulary monograph nor /a/ component of the Food and Drug Administration approved drugs, may be used in /pharmacy/ compounding under section 503A(b)(1)(A)(i)(III) of the Federal Food, Drug, and Cosmetic Act.

As of October 2, 1987 piracetam (Trade name: Nootropil) is listed on the FDA's Cumulative List of All Orphan Designated Products. Piracetam's orphan designation is for the treatment of myoclonus and its sponsor is UCB, Inc. 1950 Lake Park Drive Smyrna, GA 30080