Histamine and cognitive disorders such as schizophrenia and

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Histamine and cognitive disorders such as schizophrenia and

 

Histamine
(2-(4-imidazolyl)-ethylamine)
is a biogenic amine which produces more than one effect on four types of G-protein
coupled receptors (GPCRs). There are four different histamine receptors (H1,
H2, H3, and H4) that will maintain many types
of physiological homeostasis through their actions6. The histamine
transmitter can be found in the nervous system3. Also being a
signalling molecule, in the gut and is also involved in the immune response3.
The four histaminergic receptors have been cloned and have different expression
throughout the brain which will contribute with different behavioural patterns2.
The receptors will couple to different G proteins to initiate different
effector pathways2.  Histamine neurones are found to reside in the
tuberomamillary nucleus of the hypothalamus and their axons are distributed all
around the central nervous system3. Histamine in the brain will
facilitate wakefulness and helps with the function of different behaviours3,4.
Recent studies have suggested the deficiency of histamine in the brain may
contribute to diseases such as Parkinson’s disease and multiple sclerosis4
Histamine plays an important role in inflammatory action, intracellular
communication and common pathologies1. It has been long known that histamine plays a role
in the cause of allergic reactions and response to gastric acid secretion2.
Antihistamines such as chlorpheniramine and fexofenadine are effective at
treating allergic reactions through the histamine activation of H1
receptors6. The recent discovery of histamine in the brain has
shown to control homeostatic functions2. The actions of H1 and H2
receptors are mostly excitatory however, those of H3 are inhibitory through
their presynaptic actions4. H1 and H2 receptors have been novel
drug targets due to their highly effective responses and are beneficial agents6.

 

The
H3R first characterised as an auto receptor in 1983 but was later established
to also function as a heteroreceptor6. Through its actions, it can
also regulate the release of other neurotransmitters6. Like the
histamine family, the histamine H3 receptor is also a G-protein coupled
receptor6. Those features attributing to H3R make it an attractive
drug target for CNS disorders2. In the previous years, the
discovery of new and promising drug targets has led to the advancement of new compounds
to treats CNS disorders5. The interest in homeostatic control in
the brain was re-established due to the discovery of H3 and H4 receptors5.
The H3R has been identified as the drug target of pain, sleep-wake disorders
and cognitive disorders such as schizophrenia and Parkinson’s4,5.
There is an importance of H3 signalling in the brain to be able to store short
and long term memories which explain the development of Alzheimer’s when there
is a deficiency4. 

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