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Could an antihistamine be used for obesity?

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Think histamine and you think of allergy and stomach acid, right?  Well, as it turns out, this is only part of the picture.  There are three types of histamine receptors; H1, H2 and H3.  H1 has its main role in allergy and is the main target for traditional pharmacological antihistamines used in the treatment of allergic conditions.  H2 is the target for drugs such as ranitidine and cimetidine, used to inhibit stomach acid secretion.  But in my opinion, H3 is the receptor that poses undiscovered opportunities and is the most interesting.
Histamine is generally stored in mast cells and is released in response to a number of chemicals or mediators.  It can also be found in ECL cells in the stomach and in platelets, which increases the availability of histamine in those parts of the body with limited mast cells.
H3 occurs mainly in the CNS and stimulation of this receptor has been linked to obesity.  Enter, a pharmacist!
There must be many opportunities for targeting this receptor, but because of its two other histamine receptors, any drug that targets H3 must be as specific as possible but must also cross the blood brain barrier in order to reach its target.  Rather than blocking this receptor, would it be possible to modulate the release of histamine in the CNS by stabilising selected mast cells, rather than them all and so reducing the stimulation of H3.  Could a new drug to treat obesity really be a new antihistamine?
When thinking of new drugs and targets, care must be taken to try and predict the possible side effects, normally related to its pharmacology.  Histamine is crucial in the immune response and is released to increase the permeability of the blood vessels, allowing immune cells to the area of infection.  This then sets off an inflammatory response in order to try and protect the host from the invading infection.  This is the role of histamine that needs to be preserved, as it is essential to wellbeing but it should not be exacerbated when not necessary.
It is common, when looking at new roles for mediators or receptors, to think of them in isolation, but they are almost undoubtedly a small part of a much bigger picture.  It is essential to test these possible drug candidates in the lab, but it is only when they can be put into the body, with all its additional mediators and effects, that the true effect can be observed.  Is H3 stimulation responsible for anything else?  Would a H3 antagonist be specific to this receptor?  What other effects might it have?    This is where pharmacists can have their input and utilise their unique skill set; it’s our speciality after all.

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