145821-59-6 Usage
Description
Tiagabine hydrochloride, with the molecular formula C20H25NO2S2HCl and a molecular weight of 412.0, is a clinically useful anticonvulsant and GABA uptake inhibitor. It is a whitish, odorless, crystalline powder that was originally synthesized by Novo Nordisk Pharmaceuticals in Denmark. Tiagabine hydrochloride is a lipophilic derivative of nipecotic acid, which allows it to cross the blood-brain barrier and reach the central nervous system.
Uses
Used in Pharmaceutical Industry:
Tiagabine hydrochloride is used as an anticonvulsant for the treatment of epilepsy. It acts by inhibiting GABA transporter 1 (GAT1), blocking both neuronal and glial GABA re-uptake, which helps in controlling seizures.
Tiagabine hydrochloride is used as a treatment for anxiety disorders and panic disorder, as it helps in regulating the levels of GABA, a neurotransmitter that has a calming effect on the brain.
Used in Neuroprotective & Neuroresearch Product:
Tiagabine hydrochloride is used in the study of serotoninergic transmission in G1 cells and has been utilized to investigate its anti-aging effects on the sensory neurons of C. elegans, contributing to neuroprotective and neuroresearch applications.
Used in the form of Gabitril1:
Tiagabine hydrochloride is marketed under the brand name Gabitril1, available in tablet forms of 2, 4, 12, and 16 mg. It is used for the treatment of epilepsy and is marketed by Cephalon.
Indications
Tiagabine is licensed by the United States Food and Drug Administration (FDA) for adjunctive therapy in adults, and children of 12 years and older in the treatment of partial seizures with or without secondary generalization. There is no evidence to support a broader spectrum of action in epilepsy (Ben-Menachem 1995; Bialer et al. 2007). Tiagabine is also licensed in Europe by the European Medicines Agency (EMEA) for the same indications.
Clinical Applications
Tiagabine is currently used as adjunctive treatment in adults and children 12 years and older, suffering from partial-onset seizures, which cannot be satisfactorily controlled with other antiepileptic drugs. This indication was based on the results of five multi-center, double-blind, placebo-controlled clinical trials (two cross over and three parallel group studies) that proved its efficacy in patients with refractory partial seizures. These studies included a total of 951 adult and adolescent patients treated with add-on tiagabine at doses ranging from 16 to 56 mg compared to placebo (Ben-Menachem 1995; Richens et al. 1995; Sachdeo et al. 1997; Kalviainen et al. 1998; Uthman et al. 1998; Crawford et al. 2001). An integrated analysis of these studies demonstrated a significant 50% reduction in all seizure types in 23% of the tiagabine-treated group compared to 9% of the placebotreated group during a 7–12 week period (Ben-Menachem 1995). Doses between 32 and 56 mg in three or four divided doses were more effective than placebo (Sachdeo et al. 1997; Uthman et al. 1998). There was a dose–response relationship with greater efficacy at 56 mg/day (Uthman et al. 1998).
Drug Interactions
Tiagabine has minimal potential interaction with other drugs (Leppik et al. 1999). Tiagabine is not known to cause either induction or inhibition of hepatic microsomal enzyme systems. Consequently tiagabine does not alter the plasma concentrations of other drugs including antiepileptic drugs that undergo hepatic metabolism (Gustavson et al. 1998a, b). However, enzyme-inducing drugs accelerate the hepatic metabolism of tiagabine (So et al. 1995). There is no clinically relevant interaction between tiagabine and digoxin (Snel et al. 1998).
Originator
Gabitril,Cephalon, Inc.,USA
Therapeutic Function
Antiepileptic
Biochem/physiol Actions
Tiagabine increases the synaptic GABA and enhances the neuronal inhibition. It is effective as adjunctive treatment of epilepsy and anxiety disorders.
References
1) Schacter (1999)?A Review of the Antiepileptic Drug Tiagabine, Clin. Neuropharmacol.?22?312
2) Schwartz and Nihalani (2006)?Tiagabine in anxiety disorders, Expert Opin. Pharmacother.?7?1977
3) Novak?et al.?(2001)?Treatment of Painful Sensory Neuropathy With Tiagabine: A Pilot Study, Clin. Auton. Res.?11?357
4) Braestrup?et al.?(1990)?(R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl)nipecotic Acid Binds With High Affinity to the Brain Gamma-Aminobutyric Acid Uptake Carrier, J. Neurochem. 54 639
5) Nielsen?et al.?(1991)?Characterization of Tiagabine (NO-328), a New Potent and Selective GABA Uptake Inhibitor, Eur. J. Pharmacol.?196?257
Check Digit Verification of cas no
The CAS Registry Mumber 145821-59-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,5,8,2 and 1 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 145821-59:
(8*1)+(7*4)+(6*5)+(5*8)+(4*2)+(3*1)+(2*5)+(1*9)=136
136 % 10 = 6
So 145821-59-6 is a valid CAS Registry Number.
InChI:InChI=1/C20H25NO2S2.ClH/c1-14-7-11-24-18(14)17(19-15(2)8-12-25-19)6-4-10-21-9-3-5-16(13-21)20(22)23;/h6-8,11-12,16H,3-5,9-10,13H2,1-2H3,(H,22,23);1H/t16-;/m1./s1
