PMID: 9185237Jun 1, 1997Paper

Role of the central histaminergic neuronal system in the CNS toxicity of the first generation H1-antagonists

Progress in Neurobiology
B C Sangalli

Abstract

First-generation H1-antagonist-induced central toxicity often includes psychiatric changes, seizures and hallucinations, commonly thought to result from their central anticholinergic effects. Interference with the central functions of histamine have not been adequately addressed, despite the identification of histamine as a central neurotransmitter and neuromodulator. A synthesis of data support antagonism of H1-receptors as critical to the CNS toxicity of these drugs. The histaminergic neuronal system (HNS) is involved in a variety of global brain functions. Inherent or induced alterations in the HNS are associated with behavioral disorders. Clinical and experimental evidence support a role for the HNS in seizure protection and a relationship exits between histamine regulated systems and seizures. Histamine has important neuromodulatory influences on the central electrophysiology which underlies normal thalamocortical function. H1-antagonists block the H1-receptor-mediated reduction of a background-leakage K+ current (IKL) in central neurons. Secondary alterations in other ionic currents and alterations in synaptic responses to glutamate and GABA are produced. The non-H1 receptor-mediated effects of histamine persist in the pr...Continue Reading

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