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Histamine H3 receptor antagonists in ADHD.

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Histamine H3 receptor antagonists in ADHD.

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MK-0249 is a histamine H3 receptor antagonist.1

The H3 receptor is mainly localized in the central nervous system. The H3 receptor acts as:2

  • presynaptic autoreceptor
    • modulates histamine release
  • presynaptic heteroreceptor
    • regulates the release of other neurotransmitters such as monoamines and amino acids

Histamine H3 receptor antagonists showed positive cognitive effects3 as a result of dopamine release in PFC and ACC.4

A randomized, double-blind, placebo-controlled crossover study found no short-term efficacy of MK-0249 on ADHD symptoms in adults. As a side effect, 32% reported increased insomnia, compared with 11% for placebo. The remaining side effect rate was identical to placebo5

  1. Buoli, Serati, Cahn (2016): Alternative pharmacological strategies for adult ADHD treatment: a systematic review. Expert Rev Neurother. 2016;16(2):131-44. doi: 10.1586/14737175.2016.1135735. PMID: 26693882. REVIEW ↥

  2. Ito (2009): Histamine H3-receptor inverse agonists as novel antipsychotics. Cent Nerv Syst Agents Med Chem. 2009 Jun;9(2):132-6. doi: 10.2174/187152409788452036. PMID: 20021346. ↥

  3. Stocking, Letavic (2008): Histamine H3 antagonists as wake-promoting and pro-cognitive agents. Curr Top Med Chem. 2008;8(11):988-1002. doi: 10.2174/156802608784936728. PMID: 18673168., REVIEW ↥

  4. Vohora, Bhowmik (2012): Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer’s disease, ADHD, schizophrenia, and drug abuse. Front Syst Neurosci. 2012 Oct 23;6:72. doi: 10.3389/fnsys.2012.00072. PMID: 23109919; PMCID: PMC3478588. ↥

  5. Herring, Wilens, Adler, Baranak, Liu K, Snavely, Lines, Michelson (2012): Randomized controlled study of the histamine H3 inverse agonist MK-0249 in adult attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2012 Jul;73(7):e891-8. doi: 10.4088/JCP.11m07178. PMID: 22901359. ↥

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