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Histamine and Obesity
The role of the histaminergic system in eating habits has been established in numerous animal and human studies. Histamine is best known as an allergic / inflammatory mediator; however, peripherally - produced histamine does not penetrate the blood-brain barrier (BBB) and its activities in the brain are independent of its peripheral actions. In the brain, histamine acts as a neurotransmitter and plays a major role in eating. Histamine activation of the post-synaptic H1 receptor decreases food consumption, an activity which can be mimicked by H1 agonists. In contrast, inhibition of the H1 receptor results in increased food consumption and consequent weight gain. The pre-synaptic H3 receptor has an auto-regulatory role on histamine production. Thus, inhibition of the H3 receptor may also decrease food intake. Histamine signalling has been shown to be enhanced by estrogen: hence, it may be expected to be more effective in reproductive females1 |
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Betahistine
Betahistine, an H1 receptor agonist and partial H3 receptor antagonist, is a generic prescription drug used on a worldwide basis, except in the US, to treat Ménière's disease (vertigo). With over 35 years of treatment in more than 100 million patients, betahistine has an excellent safety profile. Moreover, a post-marketing surveillance review, to be published in November 2006, Indicates that after more than 130 million patient exposures, only about 500 reports have been filed.
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Proof Of Concept (POC) Study in Humans
Three independently conducted preliminary clinical trials suggest that the drug has potential for weight reduction, especially in obese female patients, aged under≤50, as well as for prevention of weight gain associated with anti-psychotic drug therapy.
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A double-blinded pilot study, evaluating administration of Histalean™ versus placebo for 4 weeks in 20 obese women, showed a significant weight loss and reduced fat intake in the drug treated patients. The study was conducted by Dr. Nir Barak, Obecure's Chief Scientific Officer ("CSO") and a specialist in clinical nutrition and internal medicine at the Rabin Medical Center in Israel2.
In a double-blinded, dose ranging, placebo controlled Phase II study in obese patients (male and female, aged 18-65) a post hoc analysis revealed a significant weight loss only at the high dose group and only in women under age≤50.
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An open label study, evaluating the drug when administered in conjunction with olanzapine in 3 drug-naïve psychosis patients, showed that the drug prevented the weight gain normally associated with the anti-psychotic drug3.
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1. Zhou J. et. al., J Neurophysiol, (2007) 3143-3152
2. Barak, N. Clinical Interventions (2005) 209-P
3. Poyurovsky et. al., International Clinical Psychopharmacology (2005), 101-103. |
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