CI-966 

CI-966 is a potent, selective, orally active and brain-penetrant inhibitor of the GABA transporter GAT-1, with IC₅₀s of 0.26 μM and 1.2 μM for hGAT-1, rGAT-1, respectively. CI-966 shows more than 200-fold selectivity over GAT-2, GAT-3, and BGT-3. CI-966 exhibits anticonvulsant and neuroprotective activities^[1][2][3].

IC50: 0.26 μM (hGAT-1); 1.2 μM (rGAT-1); 297 μM (rGAT-2); 333 μM (hGAT-3); 1140 μM (rGAT-3); 300 μM (hBGT-3)^[1]

CI-966 functions by selectively inhibiting GABA reuptake in neurons and glial cells^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

CI-966 produces intermediate levels of Pentylenetetrazol (PTZ)-lever responding when administered to PTZ-trained rats^[4].
CI-966 enhances gamma-aminobutyric acid action in CA1 pyramidal layer in situ. CI-966 is administered systemically by i.p. injection (5 mg/kg) in Sprague-Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there is a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region^[5].
CI-966 exhibits anticonvulsant properties in various animal models. Oral absorption of CI-966 in dogs given 1.39 mg/kg is rapid with a t_max of 0.7 hr. In rats given 5 mg/kg oral, a mean t_max of 4.0 hr is observed. Following i.v. administration of the same respective doses, elimination t_1/2 in dogs and rats averages 1.2 and 4.5 hr. Absolute oral bioavailability of CI-966 is 100% in both species^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

473.41

C₂₃H₂₁F₆NO₃

110283-79-9

O=C(C1=CCCN(CCOC(C2=CC=C(C(F)(F)F)C=C2)C3=CC=C(C(F)(F)F)C=C3)C1)O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Borden LA, et, al. Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol. 1994 Oct 14;269(2):219-24.  [Content Brief]

  [2]. Green AR, et, al. GABA potentiation: a logical pharmacological approach for the treatment of acute ischaemic stroke. Neuropharmacology. 2000 Jul 10;39(9):1483-94.  [Content Brief]

  [3]. T G Dhar, et al. Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem (IF: 7.45; Q1). 1994 Jul 22;37(15):2334-42.  [Content Brief]

  [4]. D M Grech, et al. Discriminative stimulus effects of presynaptic GABA agonists in pentobarbital-trained rats. Pharmacol Biochem Behav.1994 Jan;47(1):5-11.  [Content Brief]

  [5]. U Ebert, et al. Systemic CI-966, a new gamma-aminobutyric acid uptake blocker, enhances gamma-aminobutyric acid action in CA1 pyramidal layer in situ. Can J Physiol Pharmacol. 1990 Sep;68(9):1194-9.  [Content Brief]

  [6]. L L Radulovic, et al. Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake inhibitor, CI-966 HCl, in laboratory animals. Pharm Res. 1993 Oct;10(10):1442-5.  [Content Brief]