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Orexin receptor antagonistsA drug that blocks a receptor, stopping it from being activated.Read more → matter because insomnia can be treated by removing the brain's wake signal rather than by adding a sedative on top of it, a genuinely different strategy from older sleeping tablets. Orexins, also called hypocretins, are chemical messengers released from the lateral hypothalamusA small brain structure that controls basic functions like hunger, temperature, sleep and hormone release.Read more → (a deep brain region) that promote wakefulness and stabilise the sleep-wake switch. Their complete loss causes narcolepsy, a condition of excessive daytime sleepiness and sudden sleep attacks. Dual orexin receptor antagonists, DORAs, such as suvorexant, lemborexant and daridorexant, block orexin receptors to remove the wake signal rather than actively sedating the brain. For example, imagine a patient with chronic insomnia who has struggled with dependence on benzodiazepines in the past: a DORA offers an alternative mechanism with less dependence potential.

DORAs, dual orexin receptor antagonistsA drug that blocks a receptor, stopping it from being activated.Read more →, block both orexin receptor subtypes (OX1 and OX2), preventing orexin from maintaining wakefulness and allowing sleep to occur, rather than forcing sedation through GABA-A receptorA receptor for the calming brain chemical GABA, and the site where benzodiazepines and alcohol produce their sedating effect.Read more → enhancement as benzodiazepines and 'Z-drugs' do. Because they remove a wake-promoting signal rather than adding a sedating one, DORAs carry less dependence potential than GABAergic hypnotics. Caution is needed in narcolepsy, where orexin signalling is already deficient, since further blockade could theoretically worsen the sleep-wake instability seen in that condition. For example, imagine a patient with undiagnosed narcolepsy prescribed a DORA for reported 'insomnia': the underlying orexin deficiency makes this an unsuitable choice once recognised. In practice, this means asking about daytime sleep attacks and cataplexy (sudden loss of muscle tone triggered by emotion) before starting a DORA for insomnia.

• The peptide targeted by this drug class is produced by neurons in a specific brain region. Where are those neurons located?
• A woman starting suvorexant reports brief episodes on waking in which she cannot move, and occasional leg weakness when amused. Which adverse effect does this represent?
• A pharmacologist describes suvorexant, lemborexant and daridorexant as dual antagonistsA drug that blocks a receptor, stopping it from being activated.Read more →. Which two receptors does the word dual refer to?
• A man on suvorexant is prescribed a strong inhibitor of a liver enzyme for a fungal infection. Which consequence should the prescriber anticipate?

• DORAs (suvorexant, lemborexant, daridorexant): block the wake-promoting orexin signal, unlike benzodiazepines and Z-drugs, which enhance GABAThe brain's main calming (inhibitory) chemical messenger, boosted by benzodiazepines and alcohol.Read more →-A mediated inhibition.
• Benzodiazepines/Z-drugs, carry higher dependence and toleranceNeeding a larger dose of a drug over time to get the same effect.Read more → risk, whereas DORAs are considered to carry less dependence potential through their different mechanism.
• Narcolepsy, caused by loss of orexin-producing neurons, rather than the pharmacological orexin blockade a DORA provides.
• Melatonin receptor agonistsA drug or chemical that activates a receptor to produce an effect.Read more → (e.g. agomelatine): resynchronise circadian timing rather than blocking a wake-promoting neuropeptide system.

• That gland secretes the sleep hormone rather than this peptide.
• That nucleus supplies noradrenaline rather than this peptide.
• A seizure would not produce this combination of symptoms.
• A vascular event would not recur in this stereotyped, situational way.
• These are recognised drug effects rather than a functional disorder.

• Identify the drug, receptor, enzyme or pharmacokinetic change named in the stem.
• Translate it into the immediate mechanism before looking at the options.
• Use timing and the adverse-effect pattern to separate the nearest alternatives.
• Check whether the question asks for mechanism, clinical consequence, monitoring or management.