JNJ-26489112

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

JNJ-26489112 (JNJ26489112) 是一种广谱抗惊厥药，在啮齿类动物中表现出抗听源性、电性和化学性癫痫发作的活性。

JNJ-26489112 (JNJ26489112) is a broad-spectrum anticonvulsant that displays activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures; exhibits very weak inhibition of human CA-II (IC50=35 μM); inhibits Na+, kainate, and KCNQ2 channels to varying degrees, while moderately potentiating GABA current and inhibiting N-methyl-D-aspartic acid current, its action at several targets appears to be responsible for the observed neurostabilizing effects; shows limited seizure spread and elevated seizure threshold in preclinical animal models.Epilepsy Discontinued.

JNJ-26489112 inhibits calcium influx in response to depolarization (fluorescence-based assay) with an IC50 of 34 μM. In a whole-cell, patch-clamp experiment with low-frequency stimulation (0.07 Hz), intended to measure N-type channel activity directly, JNJ-26489112 causes a concentration-dependent increase in inhibition, with an IC50 of 70 μM. JNJ-26489112 is a KCNQ2 channel opener, particularly at -50 mV.

JNJ-26489112 (i.p.) effectively blocks chemically-induced, forelimb clonic seizures in mice ( male CF-1 albino mice) that are caused by subcutaneous bicuculine (Bic), picrotoxin (Pic), or pentylenetetrazol (PTZ), with 1-h ED50 values of 197, 189, or 109 mg/kg, respectively.In adult male rats, JNJ-26489112 (p.o; 10 mg/kg) treatment shows the Cmax, tmax, F, t1/2, and AUC (total exposure) values in plasma were 9090 ng/mL (33 μM), 53 min, 95%, 8.2 h, and 53,200 ng-h/mL. Linear, dose-related increases in exposure were observed at 10, 30, and 300 mg/kg. JNJ-26489112 (i.v.; 2 mg/kg) treatment shows the Vdss is 390 mL/kg and the CL is 96 mL/h-kg. In female beagle dogs, JNJ-26489112 (p.o; 10 mg/kg) treatment shows the Cmax, tmax, F, t1/2, and AUC values in plasma are 11,500 ng/mL (41 μM), 55 min, 83%, 20 h, and 212,000 ng-h/mL. . JNJ-26489112 (i.v.; 2 mg/kg) treatment shows the the Vdss and CL values are 630 mL/kg and 30 mL/h-kg, respectively.

JNJ26489112

Others

Other Targets

Other Targets

Neurological Disease

Epilepsy

871824-55-4

278.707

C9H11ClN2O4S

>98% (HPLC)

——

O=S(NC[C@@H]1OC2=CC=C(Cl)C=C2OC1)(N)=O

(S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide

(-20℃)

With Ice Pack

≥ 2 years