Pregabalin anticonvulsant

The story of the discovery of pregabalin (2) began in 1991, when Silverman and Taylor published a paper on the anticonvulsant effect of 3-alkyl GABA analogs (Silverman et ah, 1991). Out of this collection of compounds, 3-isobutyl GABA stood out as the most active analog in the series, which protected mice from seizures induced by corneal electroshock. 

Pfizer developed a new ligand with an unforgettable name, Trichickenfootphos (TCFP) (90), for possible production of Pregabalin (91) by asymmetric hydrogenation. Pregabalin has indications as an anticonvulsant related to the inhibitory neurotransmitter y-aminobutyric acid. 

An anticonvulsant, CI-1008, also called Pregabalin (25), was developed using the Evans oxazoli-dinone auxiliary 26 derived from (fS,2/ )-(-)-norephedrine.50 The route was scaled up to produce several hundred kilogram quantities at production and pilot plant scale and provided early clinical trial material (Scheme 23.4). 

Stahl SM. Anticonvulsants as anxiolytics, part 2 Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels. J Clin Psychiatry. 2004 65 460-1. 

In addition to being a first-line treatment for neuropathic pain and anxiety disorders, pregabalin is itself an augmenting agent to numerous other anticonvulsants in treating epilepsy... 

For neuropathic pain, tricyclic antidepressants and SNRIs as well as tiagabine, other anticonvulsants, and even opiates can augment pregabalin if done by experts while carefully monitoring in difficult cases... 

If pregabalin is added to a second sedating agent, such as another anticonvulsant, a benzodiazepine, or an opiate, the titration period should be at least a week to improve tolerance to sedation... 

Pregabalin is an anticonvulsant. The mechanism of pregaba-lin s antinociceptice and antiseizure effects is unknown. Effects may be related to high-affinity binding to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in CNS tissue. 

Pregabalin is another second-generation anticonvulsant that has recently obtained FDA approval for treatment of neurogenic pain, and several randomized placebo controlled studies have shown that this compound is efficacious in the treatment of painful diabetic neuropathy [32]. Doses between 300 and 600 mg/day have shown effect already apparent after 1 week of treatment. There are few clinically important drug interactions as there is no interference with the cytochrome 450 system. This compound requires minimal dose titration and seems easy to use. Side effects to gabapentin and pregabalin include drowsiness, dizziness and peripheral edema. 

Start treatment with second-generation anticonvulsants like gabapentin or pregabalin. 

A lactulose conjugate (105) with the anticonvulsant drug pregabaline forms spontaneously upon storage of pharmaceutical formulations containing the drug and a lactose carrier." The conjugate has been proposed for treatment of CNS disorders, such as depression or Parkinson disease." ... 

Pregabalin is an anticonvulsant produced by Pfizer and several catalysts have been developed to hydrogenate a key intermediate. First results were reported by Chirotech... 

If there is no response, or there is inadequate pain control, then an anticonvulsant such as gabapentin or pregabalin is added to the... 

A method for the analysis of the basic antiepileptic compounds felbamate, lamotrigine, carbamazepine, carbamazepine-10,11-epoxide, gabapentin, pregabalin, levetiracetam, and oxcarbazepine monohydroxy derivative (oxcarb MHD) in human plasma is described. This protocol incorporates a simplified sample preparation step followed by quantitative high performance chromatography-tandem mass spectrometry detection of commonly prescribed and monitored anticonvulsant drugs. Since polytherapy is common in epilepsy patients, use of a multiconstituent assay can improve laboratory efficiency and reduce required analytical time. 

---