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BP-294 Ste Civile Bioprojet.

¹Novartis Preclinical Research, Asthma Building 386/1035, Postfach, CH-4002 Basel, Switzerland. john_r.fozard@pharma.novartis.com

Current Opinion in Investigational Drugs (London, England : 2000)

|March 16, 2001

Summary

BP-294, a histamine H3 agonist, inhibits acetylcholine release in rats. This effect, mediated by R-alpha-methylhistamine, was dose-dependent and blocked by thioperamide, suggesting a novel therapeutic pathway.

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Area of Science:

Pharmacology
Neuroscience
Respiratory Medicine

Background:

BP-294 is a prodrug of R-alpha-methylhistamine, investigated as an antiasthmatic.
Histamine H3 agonists are being explored for various therapeutic applications.

Purpose of the Study:

To investigate the mechanism of action of R-alpha-methylhistamine, a key component of BP-294.
To determine the effect of R-alpha-methylhistamine on acetylcholine release in a relevant neural pathway.

Main Methods:

Electrical stimulation of the rat bilateral vagus nerve at 0.5 Hz.
Measurement of acetylcholine release in the presence of atropine (1 microM).
Dose-response assessment of R-alpha-methylhistamine and blockade with thioperamide.

Main Results:

R-alpha-methylhistamine demonstrated a dose-dependent inhibition of acetylcholine release.
The inhibitory effect was significantly attenuated by the histamine H3 receptor antagonist thioperamide.
This suggests a specific interaction with the histamine H3 receptor.

Conclusions:

R-alpha-methylhistamine, via histamine H3 agonism, can modulate cholinergic neurotransmission.
These findings support the potential of BP-294 as a therapeutic agent by influencing acetylcholine release pathways.

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