Overview
Pramiracetam (N-[2-[bis(1-methylethyl)amino]ethyl]-2-oxo-1-pyrrolidineacetamide, investigational code CI-879) is a pyrrolidinone acetamide from the racetam family. It emerged from a 1984 medicinal chemistry series of N-[(dialkylamino)alkyl]-2-oxo-1-pyrrolidineacetamides that were screened for reversal of electroconvulsive shock-induced amnesia in mice; the bis(1-methylethyl)aminoethyl derivative was selected for further evaluation1.
Most of the published work dates from the 1980s and 1990s and comes from rodent models. Studies have examined hippocampal high-affinity choline uptake, spatial learning in the radial arm maze, choline transport across the blood-brain barrier, cortical nitric oxide synthase activity and responses to hypobaric hypoxia2,3,4,5,6. A 2010 review groups pramiracetam with piracetam, oxiracetam, aniracetam and phenylpiracetam and notes that the modes of action of piracetam-like compounds remain poorly understood7.
Mechanism of action
As described in the research literature
As described in the research literature, the most cited mechanistic finding concerns cholinergic activity. In rats, hippocampal synaptosomes prepared from in vivo studies showed increased sodium-dependent high-affinity choline uptake (HACU) with pramiracetam, whereas piracetam and aniracetam were reported to be ineffective in the same assay2.
Other studies have examined further candidate pathways. Pramiracetam and piracetam prevented the scopolamine-induced changes in choline transport across the blood-brain barrier measured in nine rat brain regions, and both increased cerebral blood flow4. In rat cerebral cortex homogenates, pramiracetam was associated with increased neuronal nitric oxide synthase activity without a change in NOS mRNA expression, an effect not seen in the hippocampus5.
Research areas
What published studies have examined
Discovery and amnesia-reversal models
The originating structure-activity study examined a series of pyrrolidineacetamides for reversal of electroconvulsive shock-induced amnesia in mice and in a general observational test for central nervous system activity1.
Sources [1]
Cholinergic markers
Rat hippocampal synaptosomes were used to compare seven compounds reported to affect cognition on high-affinity choline uptake2. A separate study measured blood-brain barrier choline transport and cerebral blood flow in scopolamine-treated rats4.
Sources [2] [4]
Spatial learning in rats
A 16-arm radial maze task in rats was used to distinguish working memory from reference memory over seven weeks of testing; the study reported an effect on the reference memory component but not the working memory component3.
Sources [3]
Nitric oxide synthase and hypoxia models
Neuronal nitric oxide synthase activity and mRNA expression were measured in rat cortex and hippocampus, alone and after lithium chloride pretreatment5. Hippocampal afterdischarges were recorded in immature rats exposed to hypobaric hypoxia, where the authors described the action of pramiracetam as only moderate6.
Sources [5] [6]
Specifications
- Molecular formula
- C14H27N3O2
- Molecular weight
- 269.4 g/mol
- CAS number
- 68497-62-1
- Form
- Measured units with a stated amount per unit, 30 or 60 to a resealable foil pouch
- Storage
- Store in a cool, dry place in the sealed pouch, away from direct light.
- Solubility and reconstitution
- Supplied ready to use: each unit is pre-measured, so no reconstitution is required.
References
- 1
Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam.
Butler DE, Nordin IC, L'Italien YJ, et al. Journal of Medicinal Chemistry, 1984.
PubMed 6716406 ↗DOI 10.1021/jm00371a023 ↗
- 2
- 3
- 4
Reversal of scopolamine-induced alterations of choline transport across the blood-brain barrier by the nootropics piracetam and pramiracetam.
Brust P Arzneimittel-Forschung, 1989.
PubMed 2610714 ↗
- 5
Systemic administration of pramiracetam increases nitric oxide synthase activity in the cerebral cortex of the rat.
Corasaniti MT, Paoletti AM, Palma E, et al. Functional Neurology, 1995.
PubMed 8557218 ↗
- 6
The action of pramiracetam on consequences of hypobaric hypoxia is only moderate.
Maresová D, Mares P Physiological Research, 1996.
PubMed 9200217 ↗
- 7