Ретигабин

Описание

Retigabine was approved in March 2011 by the European Commission for the adjunctive treatment of partial-onset seizures in adults who have epilepsy; in June 2011, the U.S. FDA approved the same drug, known in the United States as ezogabine. Retigabine differs from all currently approved antiepileptic drugs in that it acts as a selective positive allosteric modulator (opener) of KCNQ2-5 potassium channels, which are key regulators of neuronal excitability. The discovery of retigabine was based on modification of an analgesic agent flupirtine that had serendipitously shown potent anticonvulsant activity in animal models of epilepsy. Changing a central 2,3,6-triaminopyridine to a 1,2,4-triaminobenzene decreased analgesic activity while enhancing antiepileptic activity. Retigabine (D-23129) was shown to be a broad spectrum anticonvulsant with oral activity in a variety of animal models. The mechanism of action of retigabine was discovered well after its in vivo activity was recognized. Retigabine is regulated as a Schedule V compound in the United States.

Химические свойства

Purple Solid

Использование

Retigabine is a new experimental anticonvulsant drug. It may be used as a reference standard in the determination of retigabine in biological matrices using high-performance liquid chromatography coupled with tandem mass spectrometry with positive ion atmospheric pressure chemical ionization (HPLC-APCI-MS/MS).

Определение

ChEBI: A substituted aniline that is benzene-1,2,4-triamine bearing ethoxycarbonyl and 4-fluorobenzyl substituents at positions N-1 and N-4 respectively. An anticonvulsant used to treat seizures associated with epilepsy in adults.

Общее описание

Retigabine is an antiepileptic drug, which activates neuronal KCNQ-type K+ channels by inducing a large hyperpolarizing shift of steady-state activation. Retigabine can be prepared by reductive amination of 2-ethoxycarbonylamino-5-(4-fluorobenzylamino)- nitrobenzene with 4-fluorobenzaldehyde, followed by hydrogenation in the presence of Raney nickel.

Механизм действия

Retigabine has a novel mechanism of action for an antiseizure drug, acting as positive allosteric modulator of the neuronal potassium channels KNCQ (Kv2 to 5).  Under normal physiologic conditions, KNCQ channels help establish the  neuronal resting membrane potential, by providing a continual  hyperpolarizing influence.

Клиническое использование

Retigabine is an investigational antiepileptic drug with a novel mechanism of action that involves opening of neuronal voltageactivated K+ channels that serves to stabilize the membrane potential and to control neuronal excitability. Thus, retigabine also may prove to be useful in the treatment of other diseases associated with neuronal hyperexcitability. GSK (GlaxoSmithKline) intends to permanently stop producing this product, trobalt? (retigabine) tablets (50 mg, 100 mg, 200 mg, 300 mg and 400 mg) was no longer be available after June 2017. This is due to the very limited use of the drug, not for reasons of efficacy or safety.

Побочные эффекты

Dizziness, somnolence, fatigue, confusional state, aphasia, abnormal coordination, tremor, balance disorder, memory impairment, gait disturbance, blurred vision, constipation, anxiety, psychotic disorders, paraesthesia, wt gain, nausea, dyspepsia, urinary retention and hesitation, dysuria; discolouration of ocular tissues (including the retina), skin, lips, and nails; prolongation of QT interval.