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Tiagabine

Description Generic formulation Indications Dose titration Plasma levels monitoring Cautions Adverse effects Interactions Special populations Behavioural and cognitive effects in patients with epilepsy Psychiatric use
Tiagabine
Tiagabine structure
CAS No.
115103-54-3
Chemical Name:
Tiagabine
Synonyms
TGB;no328;TIGABINE;Tiagabin;TIAGABINE;NO-05-0328;nnc-05-0328;NNC-05-0328:A-70569;Gabitril / NNC 05-328;Tiagabine 145821-59-6 /
CBNumber:
CB9761920
Molecular Formula:
C20H25NO2S2
Formula Weight:
375.55
MOL File:
115103-54-3.mol

Tiagabine Properties

Melting point:
192oC dec.
CAS DataBase Reference
115103-54-3(CAS DataBase Reference)

SAFETY

Hazard Codes  Xi
Risk Statements  36/37/38
Safety Statements  26-37/39
Hazardous Substances Data 115103-54-3(Hazardous Substances Data)

Tiagabine price

Manufacturer Product number Product description CAS number Packaging Price Updated Buy

Tiagabine Chemical Properties,Uses,Production

Description

Tiagabine is a second- generation antiepileptic drug (AED) known under the proprietary brand name of Gabitril® (Teva, Petah Tikva, Israel) in the UK and USA.

Generic formulation

MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):
  • It is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns, such as patient anxiety and risk of confusion/ dosing error.

Indications

Epilepsy: adjunctive therapy for focal seizures with or without secondary generalization that are not satisfactorily controlled by other AEDs.

Recommendations summarized from NICE (2012)
  • Seizure types: on referral to tertiary care (focal seizures), contraindicated (generalized tonic- clonic seizures, tonic/ atonic seizures, absence seizures, myoclonic seizures).
  • Epilepsy types: on referral to tertiary care (benign epilepsy with centrotemporal spikes, panayiotopoulos syndrome, late- onset childhood occipital epilepsy), contraindicated (absence syndromes, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, Dravet syndrome, Lennox– Gastaut syndrome).

Dose titration

  • Epilepsy— adjunctive therapy (with enzyme- inducing AEDs): 5–10 mg daily divided into 1 or 2 doses for 7 days, then increased by 5–10 mg daily every 7 days; usual maintenance 30– 45 mg daily divided into 2 or 3 doses.
  • Epilepsy— adjunctive therapy (without enzyme- inducing AEDs): 5–10 mg daily divided into 1 or 2 doses for 7 days, then increased by 5–10 mg daily every 7 days; usual maintenance 30– 45 mg daily divided into 2–3 doses.

Plasma levels monitoring

The inter- individual variation in liver metabolism makes Tiagabine a strong candidate for therapeutic drug monitoring. A broad reference range of 20– 200 ng/ mL has been proposed, however, the relatively short half- life of Tiagabine under most conditions means that care must be taken in drawing blood for therapeutic drug monitoring. The high binding to serum proteins further suggests that measurement of free drug concentrations may be useful. However, there has been little investigation of the relationship between serum/ plasma concentrations and therapeutic efficacy.

Cautions

  • Patients with acute porphyrias.
  • Patients with absence, myoclonic, tonic and atonic seizures (risk of exacerbation).

Adverse effects

Tiagabine can be associated with adverse effects at the level the nervous system and other systems.

Interactions

With AEDs
  • AEDs that induce hepatic enzymes (such as carbamazepine, phenytoin, phenobarbital, and primidone) enhance the metabolism of tiagabine: the plasma concentration of tiagabine may be reduced by a factor .5– 3 by concomitant use of these AEDs.
  • Tiagabine reduces the plasma concentration of valproate by about 0% (this is not considered clinically important and does not warrant a dose modification).
With other drugs
  • Cimetidine increases the bioavailability of tiagabine by about 5% (this is not considered clinically important and does not warrant a dose modification).
  • The combination of tiagabine with St John Wort (Hypericum perforatum) may lead to lower exposure and loss of efficacy of tiagabine, due to the potent induction of CYP3A4 by St John Wort, resulting in increased tiagabine metabolism. Therefore, the combination of tiagabine with St John’s Wort is contraindicated.
With alcohol/food
There are no known specific interactions between alcohol and tiagabine and there are no specific foods that must be excluded from diet when taking tiagabine. Administration with food results in a decreased rate and not extent of absorption

Special populations

Hepatic impairment
  • Reduce dose, prolong the dose interval, or both, in mild to moderate impairment.
  • Avoid in severe impairment.

Renal impairment
Renal insufficiency does not affect the pharmacokinetics of Tiagabine, therefore its dosage does not need to be modified.

Pregnancy
  • Clinical experience of the use of tiagabine in pregnant women is limited and no information on tiagabine during breastfeeding is available. Therefore, as a precautionary measure, it is preferable not to use tiagabine during pregnancy or breast- feeding unless the potential benefits of treatment outweigh the potential risks.
  • In case of tiagabine treatment during pregnancy, the dose should be monitored carefully and adjustments made on a clinical basis.

Behavioural and cognitive effects in patients with epilepsy

Treatment with tiagabine has often been associated with depression and irritability. Results from randomized double- blind, controlled trials with tiagabine as adjunctive treatment have confirmed the incidence of psychiatric problems, which can be mild- to- moderate in severity and can be reported more frequently by patients with a personal history of affective disorders, or in case of rapid initial titration. Tiagabine is characterized by a good profile in terms of cognitive adverse effects, with mild effects on concentration and memory, which can be minimized by slow initial titration.

Psychiatric use

Tiagabine has no approved indications in psychiatry and there is no conclusive evidence for its efficacy in the treatment of any behavioural problems.

Description

Gabitril was launched in Denmark for use as an add-on therapy in patients refractory to other epilepsy therapies. The compound can be synthesized in five steps beginning with a bis-thiophenyl ketone derivative to produce the (R)-(-)- enantiomer. Its anti-epileptic activity resides in its potent and selective inhibition of GABA synaptosomal uptake. Tiagabine is selective for the GAT-1 GABA transporter in neurons and glia thus enhancing inhibitory GABAergic transmission. Because it has practically no effect on other uptake or receptor systems, it has a reduced potential for neurological side-effects. In particular, it does not have the benzodiazepine-like sedative effects. It is able to cross the blood brain barrier and is considered the most potent GABA uptake inhibitor known.

Chemical Properties

White to Off-White Crystalline Solid

Originator

Novo Nordisk (Denmark)

Uses

A GABA uptake inhibitor

Definition

ChEBI: A piperidinemonocarboxylic acid that is (R)-nipecotic acid in which the hydrogen attached to the nitrogen has been replaced by a 1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl group. A GABA reuptake inhibitor, it is used (generally as the hydroc loride salt) for the treatment of epilepsy.

brand name

Gabitril

General Description

A glance at tiagabine’s structure suggests anuptake inhibitor. Reportedly, it blocks GABA reuptake asa major mode of its anticonvulsant activity. Its use isagainst partial seizures. Inhibitors of GABA transporter-1(GAT-1 inhibitors) increase extracellular GABA concentrationin the hippocampus, striatum, and cortex, therebyprolonging the inhibitory action of GABA released synaptically.Nipecotic acid is a potent inhibitor of GABA reuptakeinto synaptosomal membranes, neurons, and glialcells. However, nipecotic acid fails to cross the blood-brainbarrier following systemic administration because of itshigh degree of ionization. Tiagabine, marketed as thesingle R(-)-enantiomer, a potent GAT-1 inhibitor structurallyrelated to nipecotic acid, has an improved ability tocross the blood-brain barrier, and it has recently receivedFood and Drug Administration (FDA) approval as anAED.It is well absorbed and readily metabolized byCYP3A4 to an inactive metabolite, 5-oxo-tiagabine (oxidationof the thiophen ring) or eliminated as glucuronide ofthe parent molecule.
Over 90% of tiagabine is metabolized by CYP3A4isozymes.The primary site of metabolic attack is the oxidationof the thiophen rings leading to 5-oxo-tiagabine thatlacks anticonvulsant activity and the glucuronidation via thecarboxylic function. Thus, the plasma concentrations oftiagabine would be greatly effected by any compound thatinduces or inhibits CYP3A4.

Tiagabine Preparation Products And Raw materials

Raw materials

Preparation Products


Tiagabine Suppliers

Global( 54)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Mainchem Co., Ltd.
+86-0592-6210733
+86-0592-6210733 sales@mainchem.com CHINA 32651 55
Ascent Scientific 4401179829988
4402030 700 369 customerservice@ascentscientific.co.uk United Kingdom 280 60
LGM Pharma 1-(800)-881-8210
615-250-9817 inquiries@lgmpharma.com United States 1954 70
BOC Sciences
info@bocsci.com United States 10558 65
Beijing HuaMeiHuLiBiological Chemical 010-56205725;010-86181995
010-65763397 waley188@sohu.com China 12388 58
Candia Thamtech Company Limited 0371-86615086 18203638366 0371-86159066 13526786601
0371-86159066 sales@candiapharm.com candiazhang@candiapharm.com.candiali@candiapharm.com China 2019 60
MedChemexpress LLC 609-228-6898
609-228-5909 sales@medchemexpress.com United States 4618 58
Clearsynth Labs Limited +91-22-26355700
+91-22-26355701 info@clearsynth.com India 9769 58
Shanghai TaoSu Biochemical Technology Co., Ltd. 021-33632979
021-33632979 zijuecai@targetmol.com China 2999 58
Wuhan DKY Technology Co.,Ltd. 027-81302488 18007166089
027-81302088 info@dkybpc.com;2851686510@qq.com China 1965 58

115103-54-3(Tiagabine)Related Search:


  • (r)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylicacidhyd
  • (r)-n-(4,4-di-(3-methylthien-2-yl)but-3-enyl)nipecoticacidhydrochloride
  • 4-bis(3-methyl-2-thienyl)-3-butenyl)-1-((r)-3-piperidinecarboxylicaci
  • nnc-05-0328
  • -1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid
  • NNC-05-0328:A-70569
  • no328
  • TIAGABINE
  • TIGABINE
  • Tiagabine 145821-59-6 /
  • (3R)-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic Acid, HCl, Gabitril,
  • (3R)-1-[4,4-Bis(3-methylthiophen-2-yl)but-3-enyl]piperidine-3-carboxylic acid
  • NO-05-0328
  • TGB
  • [3R,(-)]-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]-3α-piperidinecarboxylic acid
  • Gabitril / NNC 05-328
  • 3-Piperidinecarboxylicacid, 1-[4,4-bis(3-Methyl-2-thienyl)-3-buten-1-yl]-, (3R)-
  • Tiagabin
  • GABA
  • Inhibitors
  • 115103-54-3
  • C20H25NO2S2
  • C20H26ClNO2S2
  • Intermediates & Fine Chemicals
  • Neurochemicals
  • Pharmaceuticals
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