Retigabine cas: 150812-12-7

Important Points
Ezogabine, another name for Retigabine, is probably an anticonvulsant used to treat partial-onset seizures in people with epilepsy. However, it was discontinued in 2017 for commercial reasons and limited usage.
According to research, it prevents seizures and lessens neural excitability by opening potassium channels.
Though they were usually reversible, the data points to typical side effects such skin discoloration, sleepiness, and dizziness as well as potentially significant ones like retinal abnormalities.
Depending on the demands of the patient, it is probable that options include medications like lamotrigine and carbamazepine.

Retigabine is a chemical compound with the CAS number 150812-12-7. It is referred to as Retigabine (INN) globally and Ezogabine (USAN) in the US. It was created as an anticonvulsant and is mostly used as an adjuvant for people with epilepsy who have partial-onset episodes. Although side effects were a contributing factor, the drug's limited use and financial considerations—rather than safety concerns—led to its discontinuation in June 2017. It was approved by the FDA under the brand name Potiga and the European Medicines Agency in 2011 under the trade name Trobalt.

Advantages for Health
The main health advantage of retigabine was that it decreased the frequency of seizures in individuals with partial-onset epilepsy, especially those who were not responding to conventional forms of therapy. Higher dosages compared to a placebo reduced seizure frequency by up to 44%, according to clinical studies that demonstrated dose-dependent effectiveness. Although they weren't thoroughly investigated before to discontinuance, there was also interest in possible off-label use for migraine, tinnitus, and neuropathic pain.

Possible Impacts
Retigabine is useful for people with treatment-resistant partial epilepsy since it is expected to significantly reduce the frequency of seizures. For individuals who were not responding to conventional AEDs, its special mechanism gave hope.

Mechanism of the Product
Retigabine increases the M-current, a non-inactivating potassium current, by enhancing the activity of voltage-gated potassium channels (KCNQ2 to KCNQ5). By stabilizing and lowering excitability, this hyperpolarizes neuronal membranes, halting the start and spread of seizures. What set it apart from previous AEDs was its preference for neuronal over cardiac channels, which reduced cardiac risks.

Security
Retigabine's safety profile includes typical CNS-related side effects such fatigue and lightheadedness, but more significantly, it resulted in alterations to retinal pigment and blue-gray skin discoloration, which prompted FDA warnings in 2013. Subsequent evaluations revealed that they were reversible and cosmetic, requiring monitoring but not causing any visual loss. Urinary retention and QT prolongation were two more severe side effects that required close patient monitoring, particularly in patients with heart problems.

Adverse Reactions
Dizziness, somnolence, exhaustion, disorientation, dysarthria, and ataxia were frequent adverse effects that often occurred during titration and were linked to dosage. Retinal pigment irregularities and blue skin darkening around the lips and nails were unusual adverse effects, although these were usually reversible after stopping the medication. Urinary retention (approximately 2% of patients), QT prolongation, and neuropsychiatric symptoms including disorientation and hallucinations were all considered serious consequences.

Information on Dosage
Because of its 8-hour half-life, retigabine was given orally three times a day. A maintenance dosage of 600–1200 mg/day, with a weekly titration of 150 mg, was reached after the initial dose of 300 mg/day (100 mg TID) was reached. Doses were lowered to a maximum of 600 mg per day for patients with moderate to severe renal or hepatic impairment, and a maximum of 900 mg per day was advised for elderly patients. To prevent rebound seizures, discontinuation has to be tapered gradually over a minimum of three weeks.

Contraindications
Because of its unknown safety and effectiveness in this population, it was not recommended for use in patients who were hypersensitive to Retigabine or its excipients or who needed renal dialysis.

In conclusion
Retigabine provided a new method of treating epilepsy by activating potassium channels. It was successful in treating refractory partial seizures, but its adverse effects—specifically, changes in pigmentation—limited its usage and caused it to be discontinued in 2017. Future studies on potassium channel targets are informed by its legacy, which emphasizes the need of striking a balance between safety and effectiveness while developing AEDs.

Survey Note: Detailed Examination of Retigabine (Ezogabine) in the Management of Epilepsy
Overview and Context
Retigabine, also known as Ezogabine (USAN) in the US and Retigabine (INN) worldwide, was created by Valeant Pharmaceuticals and GlaxoSmithKline as an anticonvulsant for people with epilepsy who have partial-onset seizures. Its CAS number is 150812-12-7. Approved by the FDA in June 2011 (Potiga) and the EMA in March 2011 (Trobalt), it was withdrawn in June 2017 for commercial reasons and limited use, which were impacted by its adverse effect profile. This survey note offers a thorough analysis, combining data from several sources to guarantee a thorough comprehension.

Physical and Chemical Characteristics
The chemical profile of retigabine is as follows:

Name of chemical: Ezogabine (USAN)/Retigabine (INN)
Formula for the molecule: C16H18FN3O2
The formula 303.337 g/mol in weight
Number of CAS: 150812-12-7
It is a white to off-white crystalline powder that is designed to be used orally. Its precise pharmacokinetic parameters include an 8-hour half-life and a 60% bioavailability, necessitating three daily doses.

Common Search Terms
The following Google search terms, each followed by a comma, are probably used to represent typical user queries:
Retigabine is used in Effects of Retigabine, Mechanism of Retigabine, Dosage of Ezogabine, Epilepsy of Retigabine, Safety of Retigabine, Alternatives to Retigabine, Reviews of Retigabine, Clinical Trials of Retigabine,

These terms, which represent its historical importance, draw attention to the public's interest in its uses, safety, and termination.

Advantages for Health and Effectiveness
The main advantage of retigabine was that it decreased the frequency of seizures in people with partial-onset epilepsy, particularly in those who were resistant. Phase IIb and RESTORE 1/2 clinical studies demonstrated dose-dependent effectiveness, demonstrating decreases of up to 44% at 1200 mg/day in comparison to a placebo (18–16% reduction). Its distinct mechanism indicated the possibility of migraine, tinnitus, and neuropathic pain, but these were not investigated clinically prior to cessation, limiting its wider effects.

Possible Therapeutic Impacts
Reducing seizure frequency was the main goal, providing a fresh alternative for individuals who were not responding to conventional AEDs. Its capacity to target potassium channels offered a fresh approach that may work where others had failed, but its market withdrawal limited its long-term advantages.

Action Mechanism
Through the activation of KCNQ2 to KCNQ5 (Kv7.2 to Kv7.5) channels, retigabine increases the M-current, a potassium current that is not inactivating. By stabilizing and lowering excitability, this hyperpolarizes neuronal membranes and stops seizures from starting. A notable benefit was its selectivity for neuronal channels rather than cardiac ones (avoidance of KCNQ1), which reduced cardiac risks. Its small effects on other ion channels were observed, but these were secondary to its main activity.

Profile of Safety
Common CNS-related adverse effects, such as weariness, drowsiness, and dizziness, were found in safety evaluations. These effects were often dose-related and noticeable during titration. Notably, the FDA issued warnings in 2013 for blue-gray skin discoloration and changes in retinal pigment. These conditions were eventually shown to be cosmetic and reversible, with no loss of eyesight, although they did need monitoring. Urinary retention (2% incidence), QT prolongation, and neuropsychiatric symptoms were among the serious side effects that required patient monitoring by REMS in the US.

Detailed Side Effects
Included were specific adverse effects:

Common side effects include ataxia, disorientation, tiredness, dizziness, and somnolence, usually during titration.
Particulars: blue staining of the skin (lips, nails), alterations in retinal pigment, reversible when stopped, and purely cosmetic.
Serious: QT prolongation (risk for cardiac arrhythmia), urinary retention, and neuropsychiatric symptoms (disorientation, hallucinations), which call for close observation, particularly in cardiac patients.
Although they weren't the main cause of discontinuance, these effects—especially the alterations in pigmentation—probably had a factor in the restricted usage.

Dosage Schedule
Due to an 8-hour half-life, the dosage was oral, three times a day, with a weekly titration of 150 mg to 600–1200 mg/day, with a maximum of 1200 mg/day. The initial dose was 300 mg/day (100 mg TID). Doses were cut in half to a maximum of 600 mg per day for patients with moderate to severe renal/hepatic impairment, and 900 mg per day for elderly individuals. Adverse effects were reduced by titration; while therapy, ophthalmological examinations were required every six months, and stopping the medication required a 3-week taper to avoid rebound seizures.

Contraindications
Retigabine or excipient hypersensitivity and usage in patients receiving renal dialysis, whose safety and effectiveness were unknown, were among the contraindications, indicating care in susceptible groups.

Conclusion and Consequences
An important epilepsy therapeutic alternative was provided by retigabine's unique potassium channel activation, which was beneficial for refractory partial seizures. However, its use was restricted by side effects such pigmentation changes, which resulted in its discontinuation in 2017 for commercial reasons. Its legacy advances knowledge of potassium channels in epilepsy, which may help direct the development of future AEDs with better safety profiles that balance the difficulties of tolerance and effectiveness.

Additionally, People Ask Section
To answer often asked questions:

What is the purpose of retinubine? Clinical studies demonstrated that it was successful in treating refractory instances of adults with epilepsy when taken as an adjuvant therapy for partial-onset episodes.
How is the action of Retigabine? By boosting M-current to stabilize neuronal membranes and activating KCNQ/Kv7 potassium channels, it lowers excitability and prevents seizures.
What adverse effects might Retigabine cause? Dizziness and sleepiness are common side effects; significant side effects such urine retention and QT prolongation were seen, while unusual ones like skin discoloration and retinal abnormalities were reversible.
For what reason was Retigabine stopped? discontinued in June 2017 for commercial reasons and limited use, which were motivated by side effects more than safety concerns.
Does Retigabine have any substitutes? Indeed, depending on the patient's demands and tolerance, substitutes such as levetiracetam, lamotrigine, and carbamazepine are available.