Chemistry:Pirepemat

From HandWiki

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.[1][2][3][4][5][6] It has been referred to as a "nootrope" (i.e., nootropic or cognitive enhancer).[7]

Pharmacology

Pirepemat shows affinity for several neurotransmitter receptors and transporters.[8][9][4] 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][4] 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).[4] The drug was an antagonist or inhibitor at all assessed targets (which included some but not all of the preceding sites).[8][9][4]

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.[1][4] Serotonin 5-HT7 receptor antagonism and α2-adrenergic receptor antagonism were hypothesized to underlie these effects.[9][4] 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][4]

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][1][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)

References

  1. ↑ 1.0 1.1 1.2 "Treatment of Apathy in Parkinson's Disease and Implications for Underlying Pathophysiology". J Clin Med 13 (8): 2216. April 2024. doi:10.3390/jcm13082216. PMID 38673489. 
  2. ↑ "Parkinson Disease Dementia Management: an Update of Current Evidence and Future Directions". Current Treatment Options in Neurology (Springer Science and Business Media LLC) 25 (5): 93–119. May 2023. doi:10.1007/s11940-023-00749-4. ISSN 1092-8480. 
  3. ↑ "Parkinson's disease therapy: what lies ahead?". J Neural Transm (Vienna) 130 (6): 793–820. June 2023. doi:10.1007/s00702-023-02641-6. PMID 37147404. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 "(3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752) -a Novel Cortical-Preferring Catecholamine Transmission- and Cognition-Promoting Agent". J Pharmacol Exp Ther 374 (3): 404–419. September 2020. doi:10.1124/jpet.120.000037. PMID 32605972. 
  5. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Rein-HedinSjöbergWaters2021
  6. ↑ 6.0 6.1 6.2 "A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia". Mov Disord 35 (6): 1046–1054. June 2020. doi:10.1002/mds.28020. PMID 32198802. 
  7. ↑ 7.0 7.1 "Proposed INN: List 123 International Nonproprietary Names for Pharmaceutical Substances (INN)". WHO Drug Information 34 (2). 2020. https://www.who.int/docs/default-source/international-nonproprietary-names-(inn)/pl123.pdf. 
  8. ↑ 8.0 8.1 8.2 8.3 "Pirepemat". 13 September 2024. https://synapse.patsnap.com/drug/3f933680c9a84ab0bda8400c3cbd08d7. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 "Pirepemat (IRL-752) - Integrative Research Laboratories". AdisInsight. Springer Nature Switzerland AG. 26 September 2024. https://adisinsight.springer.com/drugs/800044794. 
  10. ↑ "A Systematic Review of Pharmacological Interventions for Apathy in Aging Neurocognitive Disorders". Brain Sci 13 (7): 1061. July 2023. doi:10.3390/brainsci13071061. PMID 37508993. 
  11. ↑ IRLAB Therapeutics AB (3 August 2020). "IRLAB's IRL752 is proposed pirepemat as a unique INN by WHO". https://www.prnewswire.com/news-releases/irlabs-irl752-is-proposed-pirepemat-as-a-unique-inn-by-who-301104526.html. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Pirepemat&oldid=4308882"