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Pregabalin – Alpha-2-Delta Mechanism — SCE Neurology MCQ

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ModerateMultiple Sclerosis & CNS InflammationPregabalin – Alpha-2-Delta MechanismSCE Neurology

A 50-year-old woman with MS has chronic neuropathic pain in her legs. Her neurologist prescribes pregabalin. What is the mechanism of action of pregabalin?

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Correct answer: B — Pregabalin binds to the alpha-2-delta subunit of voltage-gated calcium channels, reducing calcium influx at nerve terminals and decreasing release of excitatory neurotransmitters (glutamate, noradrenaline, substance P) — thereby reducing neuropathic pain signalling

Pregabalin (and gabapentin) bind to the alpha-2-delta subunit of presynaptic voltage-gated calcium channels. This reduces calcium-dependent release of excitatory neurotransmitters (glutamate, noradrenaline, substance P) from hyperexcitable neurons, damping down neuropathic pain signalling. Despite the name 'gabapentinoid', they do NOT directly affect GABA receptors or GABA metabolism. A: Sodium channel blockade is the mechanism of carbamazepine/lamotrigine. C: GABA reuptake inhibition is tiagabine. D: Opioid agonism is morphine. E: NMDA antagonism is amantadine/ketamine.

Reference: BNF – Pregabalin; NICE CG173