Chemical compound
Pharmaceutical compound
Tulrampator Clinical data Other names S-47445; CX-1632 Identifiers 8-cyclopropyl-3-[2-(3-fluorophenyl)ethyl]-7H -[1,3]oxazino[6,5-g][1,2,3]benzotriazine-4,9-dione
CAS Number PubChem CID ChemSpider UNII ChEMBL CompTox Dashboard (EPA) Chemical and physical data Formula C 20 H 17 F N 4 O 3 Molar mass −1 3D model (JSmol ) InChI=1S/C20H17FN4O3/c21-13-3-1-2-12(8-13)6-7-25-20(27)15-10-18-16(9-17(15)22-23-25)19(26)24(11-28-18)14-4-5-14/h1-3,8-10,14H,4-7,11H2
Key:JHCFQXNWYDLBOG-UHFFFAOYSA-N
Tulrampator (developmental code namesS-47445 ,CX-1632 ) is apositive allosteric modulator (PAM) of theAMPA receptor (AMPAR), anionotropic glutamate receptor , which is under development byRespireRx Pharmaceuticals (formerly Cortex Pharmaceuticals) andServier for the treatment ofmajor depressive disorder (as anadjunct ),Alzheimer's disease ,dementia , andmild cognitive impairment .[ 1] [ 2] [ 3] [ 4] phase II clinical trial for depression, but failed to show superiority over placebo.[ 5] phase I trials for dementia and mild cognitive impairment.[ 2]
Tulrampator is a "high-impact" AMPAR potentiator,[ 6] CX-516 and itscongener farampator (CX-691, ORG-24448), and is able to elicit more robust increases in AMPAR activation.[ 7] cognition andmemory at low doses, but producemotor coordination disruptions ,convulsions , andneurotoxicity at higher doses.[ 8] antidepressant -,antianhedonic -, andanxiolytic -like effects, and to haveneurotrophic andneuroplasticity -promoting activities.[ 3] [ 4] brain-derived neurotrophic factor (BDNF) in thehippocampus and to stimulate hippocampalneurogenesis .[ 3] [ 9]
The rapidly-actingantidepressant effects of theNMDA receptor antagonist ketamine appear to be mediated through indirect/downstream activation of AMPARs.[ 3] AMPAR antagonist NBQX .[ 3] dissociative /hallucinogenic and certain otheradverse effects (e.g.,urotoxicity ).[ 3]
^ "Tulrampatorum" (PDF) .WHO Drug Information .30 (4): 684. 2016-12-19. Retrieved2017-08-31 .[dead link ^a b "S 47445" .AdisInsight . Retrieved2017-08-31 .^a b c d e f Mendez-David I, Guilloux JP, Papp M, Tritschler L, Mocaer E, Gardier AM, Bretin S, David DJ (2017)."S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms" .Front Pharmacol .8 : 462.doi :10.3389/fphar.2017.00462 PMC 5515821 PMID 28769796 . ^a b Giralt A, Gómez-Climent MÁ, Alcalá R, Bretin S, Bertrand D, María Delgado-García J, Pérez-Navarro E, Alberch J, Gruart A (2017)."The AMPA receptor positive allosteric modulator S 47445 rescues in vivo CA3-CA1 long-term potentiation and structural synaptic changes in old mice" .Neuropharmacology .123 :395– 409.doi :10.1016/j.neuropharm.2017.06.009 hdl :2445/160592 PMID 28603025 . ^ "Synopsis" (PDF) .^ "Patent US9700596 - Locally released growth factors to mediate motor recovery after stroke - Google Patents" .google.com . Retrieved2017-08-31 .^ Roberts BM, Holden DE, Shaffer CL, Seymour PA, Menniti FS, Schmidt CJ, Williams GV, Castner SA (2010). "Prevention of ketamine-induced working memory impairments by AMPA potentiators in a nonhuman primate model of cognitive dysfunction".Behav. Brain Res .212 (1):41– 8.doi :10.1016/j.bbr.2010.03.039 .PMID 20347881 .S2CID 9432930 . ^ Ranganathan M, DeMartinis N, Huguenel B, Gaudreault F, Bednar MM, Shaffer CL, Gupta S, Cahill J, Sherif MA, Mancuso J, Zumpano L, D'Souza DC (2017). "Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242".Mol. Psychiatry .22 (11):1633– 1640.doi :10.1038/mp.2017.6 .PMID 28242871 .S2CID 3691566 . ^ Calabrese F, Savino E, Mocaer E, Bretin S, Racagni G, Riva MA (2017)."Upregulation of neurotrophins by S 47445, a novel positive allosteric modulator of AMPA receptors in aged rats" (PDF) .Pharmacol. Res .121 :59– 69.doi :10.1016/j.phrs.2017.04.019 PMID 28442348 .
AMPAR Tooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor KAR Tooltip Kainate receptor NMDAR Tooltip N-Methyl-D-aspartate receptor
