Abecarnil

Abecarnil (ZK 112119) is a ligand or a partial agonist for benzodiazepine (BZ) receptor. Abecarnil possesses anxiolytic and anticonvulsant properties. Abecarnil can act as a positive allosteric modulator of GABAA receptor. Abecarnil inhibits the binding of the BZ [3H]lormetazepam to rat cerebral cortex membranes, with an IC50 of 0.82 nM. Abecarnil can be used for epilepsy research[1][2][3][4].

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

Abecarnil enhances the binding of t-[35S]butylbicyclophosphorothionate to rat cortical membranes[1]. Abecarnil exhibits a 3- to 6-fold higher affinity to forebrain BZ receptors than Diazepam (DZP)[1].

Abecarnil (0.3 mg/kg, IP, once) antagonizes the brain neuroactive steroid increase induced by foot shock[2]. Abecarnil (0-2.5 mg/kg, IP, once) dose dependently reduces epileptic activity[3]. Abecarnil is effective against sound-induced convulsions in DBA/2 mice, against air blast-induced generalized seizures in gerbils and against myoclonus in baboons Papio papio[4]. Abecarnil is 2-10 times more potent than DZP in most rodent tests of anxiolytic activity, and in reducing locomotor activity in mice and rats thoroughly habituated to the test chamber[1]. Animal Model: Male Sprague-Dawley CD rats (200-250 g)[2] Dosage: 0.3 mg/kg Administration: IP, once, given 30 min before sacrifice Result: Failed to change the basal pregnenolone and progesterone, while only slightly decreased THDOC levels, but antagonized the brain neuroactive steroid increase induced by foot shock. Animal Model: WAG/Rij rats (male and female, 190-380 g, age 13-19 weeks, 8 rats each group)[3] Dosage: 0, 0.16, 0.4, 1.0, and 2.5 mg/kg; 1 mL/400 g Administration: IP, once Result: Reduced the duration of spike-wave discharges and increased immobile behavior. Dose dependently reduced epileptic activity, whether measured as number, mean duration, or total duration of spike-wave discharges. The ED50 for reducing the number of spike-wave discharges in the second hour was 0.4 mg/kg.

[1]. Stephens DN, et al. Abecarnil, a metabolically stable, anxioselective beta-carboline acting at benzodiazepine receptors. J Pharmacol Exp Ther. 1990 Apr;253(1):334-43.

[2]. Barbaccia ML, et al. Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil. Pharmacol Biochem Behav. 1996 May;54(1):205-10.

[3]. Coenen AM, et al. Effects of the beta-carboline abecarnil on epileptic activity, EEG, sleep and behavior of rats. Pharmacol Biochem Behav. 1992 Jul;42(3):401-5.

[4]. Turski L, et al. Anticonvulsant action of the beta-carboline abecarnil: studies in rodents and baboon, Papio papio. J Pharmacol Exp Ther. 1990 Apr;253(1):344-52.

MOLECULAR FORMULA :

C24-H24-N2-O4

MOLECULAR WEIGHT :

404.50

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

571 ug/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions

REFERENCE :

BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year: 35,386,1993