HISTAMINE RECEPTORS H1, H2, H3 And Neurotransmitter / Hormone Release.
The concept of histamine modulation has a long history, from H1 antagonists in the treatment of bronchial constriction, and alleviating allergy symptoms, to stomach acid pills with documented CNS effects and disturbances, Then there's the H(3) receptor, and it's complex actions in the brain and nervous system. H3 antagonists are being investigated with promising results in treating ADHD, Schizophrenia and Alzheimer's Disease......
They also are KEY players in Sympathetic Nervous Stimulation....H3 activation depresses the nervous system but ironically can cause anxiety and attention issues by the same mechanism - that is reducing GABA and serotonin release, as well as dopamine,glutamate and acetylcholine.
Since they play a role as autoreceptors, both inhibiting histamine release and separately on monoamine nerve terminals, inhibiting release, I could define this receptor as the most "nasty" receptor in the book of human biology. While H(3) agonists can improve sleep, the overall effects on cognition wouldn't be worth it. Luckily, there are no H3 agonists directly available.
H3 antagonism also is one mechanism to restore dopamine production in the brain - and increasing D(2) mRNA expression.
This means that H3 antagonism can potentiate dopaminergic drugs and help treat Parkinson's Disease and tremors. Interesting, I guess it's a paradoxical effect in terms of H3 agonist clinical use. Most of us don't realize what we are doing to our body and prefer to see only the positive in things, with a lack of awareness coupled to it.
H3 antagonism raises dopamine - but interestingly blunts psychotic symptoms. My theory (and based on science) is that the cyclic AMP and GABA release caused by H3 antagonism creates an anxiolytic/focused state where erratic behavior and delirium is reduced due to normalizing CNS function. It's well documented that cyclic AMP is the key player in psychotic states, and D2 antagonists (antipsychotics) which raise cyclic AMP stand as one example - but they also cause a lot of terrible side-effects.
http://www.ncbi.nlm..../pubmed/6294425
Schizophrenia and reduced cyclic AMP production: evidence for the role of receptor-linked events.AbstractReduced cyclic AMP (cAMP) production has been found in platelets of schizophrenic patients. cAMP is generated physiologically as a result of a series of steps beginning with receptor activation by a ligand, progressing through activation of the enzyme protein, adenylate cyclase. The deficit of cAMP found in the schizophrenic population may occur at any one, or at multiple steps in this cascade. The present study attempts to discriminate whether impaired adenylate cyclase itself was responsible for the cAMP deficit or whether abnormalities in receptor events or linkage are present in schizophrenics. The production of cAMP following direct stimulation of adenylate cyclase by NaF was contrasted with receptor mediated activation of adenylate cyclase by prostaglandin E1 (PGE1) in disrupted platelet preparations from schizophrenics and normal controls. cAMP formation stimulated by NaF was not different in platelets of schizophrenics as compared to controls, however, platelets of schizophrenics showed reduced response to PGE1 stimulation. The authors interpret these findings as evidence for a membrane associated abnormality of either receptor or receptor-adenylate cyclase linkage in the schizophrenias.
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Going back to memory function....now what chemical is normally deficient in Dementia/Alzheimer's Patients? OH...that's right...Acetylcholine - and this is also inhibited by Histamine H(3)'s.
That would explain alot, and ADHD is also correlated with low acetylcholine levels.
http://www.ncbi.nlm....pubmed/16273023
The interplay of neurotransmitters in Alzheimer's disease.AbstractEvidence exists for both cholinergic and glutamatergic involvement in the etiology of Alzheimer's disease. Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer's disease. This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer's disease. The glutamatergic hypothesis links cognitive decline in patients with Alzheimer's to neuronal damage resulting from overactivation of N-methyl-d-aspartate (NMDA) receptors by glutamate. The sustained low-level activation of NMDA receptors, which are pivotal in learning and memory, may result from deficiencies in glutamate reuptake by astroglial cells in the synaptic cleft. This article reviews the roles of ACh and glutamate in Alzheimer's disease, with particular attention given to the overlap between cholinergic and glutamatergic pathways. In addition, the potential synergy between cholinesterase inhibitors and the NMDA receptor antagonist memantine in correcting neurologic abnormalities associated with Alzheimer's disease is addressed.
http://www.nel.edu/2...05R04_Paclt.pdf
Front Syst Neurosci. 2012 Oct 23;6:72. doi: 10.3389/fnsys.2012.00072. eCollection 2012. Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer's disease, ADHD, schizophrenia, and drug abuse.AbstractHistamine 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.
KEYWORDS:ADHD; Alzheimer's disease; drug abuse; histamine H3 receptor; schizophrenia
PMID: 23109919 [PubMed] PMCID: PMC3478588 Free PMC Article
Edited by Area-1255, 31 August 2014 - 11:47 PM.
