Pesampator
Chemical compound
From Wikipedia, the free encyclopedia
Pesampator (INN; developmental code names BIIB-104 and PF-04958242) is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which was under development by Pfizer for the treatment of cognitive symptoms in schizophrenia.[1][2][3] In March 2018, the development of the drug was transferred over from Pfizer to Biogen.[4] It was also under development for the treatment of age-related sensorineural hearing loss, but development for this indication was terminated due to insufficient effectiveness.[3][5] In July 2022, Biogen discontinued the development of pesampator for cognitive symptoms in schizophrenia due to ineffectiveness.[6]
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| Other names | BIIB-104; PF-04958242 |
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| Formula | C18H20N2O4S2 |
| Molar mass | 392.49 g·mol−1 |
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Pesampator belongs to the biarylpropylsulfonamide group of AMPAR PAMs, which also includes LY-404187, LY-503430, and mibampator (LY-451395) among others.[7] It is described as a "high-impact" AMPAR PAM, unlike so-called "low-impact" AMPAR PAMs like CX-516 and its congener farampator (CX-691, ORG-24448).[2] In animals, low doses of pesampator have been found to enhance cognition and memory, whereas higher doses produce motor coordination disruptions and convulsions.[2] The same effects, as well as neurotoxicity at higher doses, have been observed with orthosteric and other high-impact allosteric AMPAR activators.[2]
In healthy volunteers, pesampator has been found to significantly reduce ketamine-induced deficits in verbal learning and working memory without attenuating ketamine-induced psychotomimetic effects.[2] It was able to complete reverse ketamine-induced impairments in spatial working memory in the participants.[2]
In addition to its actions on the AMPAR, pesampator has been reported to act as a GlyT1 glycine transporter blocker.[8][9] As such, it is also a glycine reuptake inhibitor, and may act indirectly to activate the glycine receptor and the glycine co-agonist site of the NMDA receptor by increasing extracellular levels of glycine.[8][9]