A review of recent progress in pregabalin synthesis

Pregabalin is an anticonvulsant drug and works by slowing down the nerve impulses that cause seizures. Pregabalin also affects substances in the brain that transmit pain signals in the nervous system, This drug is used to reduce pain from fibromyalgia, nerve pain in people with diabetes (diabetic nerve damage), herpes zoster, and spinal cord injuries(Scheme ۱) [۱'۲'۳].Pregabalin binds to the alpha-۲-delta ( ۲- ) subunit of voltage-dependent calcium channels within the CNS and modulates calcium influx in nerve terminals, thereby inhibiting the release of excitatory neurotransmitters including glutamate, norepinephrine (noradrenaline), serotonin, Dopamine, substance P. Although structurally related to GABA, it does not bind to GABA or benzodiazepine receptors. Performs analgesic and anticonvulsant activities. Pregabalin may also affect noradrenergic and descending serotonergic pain transmission pathways from the brainstem to the spinal cord [۴, ۵].The structure and function of voltage-gated calcium channel subunits are illustrated by a schematic diagram of a single calcium channel, including the four homologous domains of the calcium channel ۱ subunit (I-IV), the extracellular ۲ and linked subunits comprising the ۲- protein with a single transmembrane domain (red), the completely cytosolic subunit (rose) and the less well characterized subunit (green) along with the binding site for Pregabalin is shown [۶, ۷]. (Scheme ۲)

Keywords:

S-pregabalin , Synthesis , Enantiomer separation