Neuropsychiatry of Histaminergic Circuits: Potential Role of Novel H3 Receptor Selective Antagonist/ Inverse Agonist Pitolisant in Prader-Willi Syndrome

Histamine and its receptors have been implicated in several neuropsychiatric conditions including Gilles de la Tourette syndrome, schizophrenia, attention deficit hyperactivity disorder, narcolepsy, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, epilepsy, and substance use disorders.1–3 Histaminergic brain circuitry is involved in multiple complex neurological functions including the arousal system, sensory and motor functions, attentional processes, memory, learning and reward.2 Histamine is synthesized from the amino acid histidine which is taken up into histamine neurons and converted by histidine decarboxylase into histamine.2 The histaminergic neurons are located in the tuberomammillary nucleus of the posterior hypothalamus, with widespread projections innervating most areas of the brain.2 There are 4 different types of histamine receptors (H1R-H4R), all of them are part of the rhodopsin-like family of G protein-coupled receptors.