Pirepemat
Experimental cognitive enhancer
From Wikipedia, the free encyclopedia
Pirepemat (INN; developmental code name IRL752 or IRL-752) is a drug which is under development for the prevention of falls in people with Parkinson's disease and Parkinson's disease dementia.[2][3][4][5][1][6] It has been referred to as a "nootrope" (i.e., nootropic or cognitive enhancer).[7]
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| Other names | IRL-752; IRL752 |
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| Elimination half-life | 3.7–5.2 hours[1] |
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| Formula | C11H13F2NO |
| Molar mass | 213.228 g·mol−1 |
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Pharmacology
Pirepemat shows affinity for several neurotransmitter receptors and transporters.[8][9][5] These include the serotonin 5-HT7 receptor (Ki = 980 nM), the sigma σ1 receptor (Ki = 1,200 nM), the serotonin transporter (SERT) (Ki = 2,500 nM), the α2C-adrenergic receptor (Ki = 3,800 nM), the α2A-adrenergic receptor (Ki = 6,500 nM), the serotonin 5-HT2C receptor (Ki = 6,600 nM), the serotonin 5-HT2A receptor (Ki = 8,100 nM), and the norepinephrine transporter (NET) (Ki = 8,100 nM).[8][9][5] It also shows affinity for the rat κ-opioid receptor (KOR) (Ki = 6,500 nM) and has weak affinity for the α1-adrenergic receptor (Ki = 21,000 nM).[5] The drug was an antagonist or inhibitor at all assessed targets (which included some but not all of the preceding sites).[8][9][5]
Pirepemat has been described as a "cortical enhancer" and has been reported to region-specifically increase norepinephrine, dopamine, and acetylcholine levels in the cerebral cortex.[2][5] Serotonin 5-HT7 receptor antagonism and α2-adrenergic receptor antagonism were hypothesized to underlie these effects.[9][5] In animals, pirepemat has been found to reverse hypoactivity induced by the dopamine depleting agent tetrabenazine whilst not increasing basal locomotor activity and not affecting or minimally influencing dextroamphetamine- and dizocilpine-induced locomotor hyperactivity.[6][5]
Clinical trials
The drug was reported to improve motivation and reduce apathy in people with Parkinson's disease in a phase 2a clinical trial.[10][2][6]
As of September 2024, pirepemat is in phase 2 clinical trials for Parkinson's disease.[9][8] A phase 3 trial is being planned.[9] The drug was also under development for the treatment of "behavioral disorders" and attention deficit hyperactivity disorder (ADHD).[9] However, no recent development for the former indication has been reported and development for ADHD was discontinued.[9] In August 2020, pirepemat received an INN with a novel suffix reflecting its reputedly new and unique mechanism of action.[11][7] Pirepemat is under development by Integrative Research Laboratories (IRLAB).[9]
See also
- List of investigational Parkinson's disease drugs
- Motivation-enhancing drug
- Linepemat (possibly IRL757)
- Mesdopetam (IRL790)