Pesampator

Pesampator (INNTooltip International Nonproprietary Name; 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]

Pesampator

Clinical data
Other names	BIIB-104; PF-04958242
Identifiers
IUPAC name N-[(3S,4S)-4-[4-(5-cyanothiophen-2-yl)phenoxy]oxolan-3-yl]propane-2-sulfonamide
CAS Number	1258963-59-5
PubChem CID	49853967
ChemSpider	32698813
UNII	9G1A824CC2
CompTox Dashboard (EPA)	DTXSID001337272
Chemical and physical data
Formula	C18H20N2O4S2
Molar mass	392.49 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)S(=O)(=O)N[C@H]1COC[C@H]1OC2=CC=C(C=C2)C3=CC=C(S3)C#N
InChI InChI=1S/C18H20N2O4S2/c1-12(2)26(21,22)20-16-10-23-11-17(16)24-14-5-3-13(4-6-14)18-8-7-15(9-19)25-18/h3-8,12,16-17,20H,10-11H2,1-2H3/t16-,17+/m0/s1 Key:TTYKUKSFWHEBLI-DLBZAZTESA-N

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]

See also

• AMPA receptor positive allosteric modulator
• List of investigational antipsychotics