Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer's disease, ADHD, schizophrenia, and drug abuse

Abstract

Histamine H3 receptor (H3R) antagonists/inverse agonists possess potential to treat diverse disease states of the central nervous system (CNS). Cognitive dysfunction and motor impairments are the hallmark of multifarious neurodegenerative and/or psychiatric disorders. This review presents the various neurobiological/neurochemical evidences available so far following H3R antagonists in the pathophysiology of Alzheimer's disease (AD), attention-deficit hyperactivity disorder (ADHD), schizophrenia, and drug abuse each of which is accompanied by deficits of some aspects of cognitive and/or motor functions. Whether the H3R inverse agonism modulates the neurochemical basis underlying the disease condition or affects only the cognitive/motor component of the disease process is discussed with the aim to provide a rationale for their use in diverse disease states that are interlinked and are accompanied by some common motor, cognitive and attentional deficits.

Heteromeric Dopamine Receptor Signaling Complexes: Emerging Neurobiology and Disease Relevance

“…Conversely, both D1R and H3R antagonists attenuated D1R-or H3R-induced ERK activation (Moreno et al, 2011). As the H3R has been implicated in a number of psychiatric disorders, including schizophrenia, addiction, and ADHD (Vohora and Bhowmik, 2012), these findings suggest a potential contribution of the D1-H3 heteromer in mediating some of the effects attributed solely to the H3R, and thus further investigation into the role of the D1-H3 heteromer in the etiology of these mental health disorders is warranted.…”

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

“…Furthermore, H 3 heteroreceptors are also located on non-histaminergic neurons, regulating release of neurotransmitters such as acetylcholine, serotonin and dopamine, and may also be involved in food intake regulation [78,42,80,81]. However, SGAs maintain a very weak antagonistic potency at histaminergic H 3 Rs in the brain [82,83]. As a result, H 3 R may play an indirect role in regulating the weight gain/obesity side-effects induced by SGAs.…”

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice

“…Importantly, we found that the inhibition of the H 3 R does not alter the motivational state of mice to drink nonalcohol tastants such as saccharin, which is a critical issue from a potential therapeutic development perspective. Our findings therefore suggest that antagonists of the H 3 R pathway, which are actively being developed for the treatment of several psychiatric disorders [24,[57][58][59][60], are potential pharmacological candidates that could be developed for the treatment of alcohol use and abuse disorders.…”