Agomelatine Pharmacology — MRCPsych Paper B MCQ
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Correct answer: A — MT1 and MT2 receptor agonism with 5-HT2C receptor antagonism
Explanation lettering: B = shown as A · A = shown as B · D = shown as C · E = shown as D · C = shown as E
B is correct. Agomelatine combines agonism at the MT1 and MT2 melatonin receptors with antagonism at the 5-HT2C receptor. Melatonergic agonism contributes to resynchronisation of circadian rhythms, while 5-HT2C antagonism is associated with increased noradrenaline and dopamine release in the frontal cortex. It does not act by inhibiting monoamine reuptake. Option A reverses both actions. Options C and E incorrectly substitute 5-HT2A antagonism, while D incorrectly attributes 5-HT1A partial agonism. Although not part of its mechanism, hepatotoxicity is an important prescribing consideration: liver function testing is required before treatment and periodically during treatment.
Reference: electronic Medicines Compendium, Valdoxan 25 mg film-coated tablets: Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, updated 30 April 2026. https://www.medicines.org.uk/emc/medicine/21830/SPC/valdoxan