Dataset Information

Proxyfan acts as a neutral antagonist of histamine H3 receptors in the feeding-related hypothalamic ventromedial nucleus.

ABSTRACT:

Background and purpose

Centrally acting histamine H(3) receptor ligands are proposed as potential treatments for obesity, although the value of inverse agonists at these receptors is still debated. Functional inhibition of H(3) autoreceptors activates neurones in a hypothalamic 'satiety' centre. The H(3) receptor antagonist, proxyfan was used as a tool to assess the action of histaminergic compounds in this model.

Experimental approach

We compared the actions of histamine on feeding with those of an H(3) receptor agonist (imetit) and inverse agonist (thioperamide) in rats and mice. Sites of action were identified by immunohistochemistry and the hypothalamic ventromedial nucleus (VMN) was investigated using electrophysiological techniques.