Clobenpropit is a selective histamine H3 receptor antagonist (Ki = 0.17 nM in rat cortical membranes).[1] Clobenpropit (0.3, 0.1, and 3 nM) reduces inhibition of electrically induced contractions in isolated guinea pig ileum longitudinal muscle by the H3 receptor agonist (R)-α-methylhistamine. It does not inhibit histamine-induced contractions in isolated guinea pig ileum or tachycardia in isolated right atria at concentrations up to 1 μM, indicating a lack of functional antagonist activity at H1 and H2 receptors, respectively. Clobenpropit (1 and 3 mg/kg) decreases the duration of the tonic, clonic, and convulsive coma phases of electrically induced convulsions in mice, an effect that can be blocked by (R)-α-methylhistamine or imetit.[2] Clobenpropit (0.1 μM) also increases GABA release and inhibits NMDA-induced neurotoxicity in primary rat cortical neurons.[3]
Reference:
[1]. Solt, L.A., Kumar, N., Nuhant, P., et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 472(7344), 491-494 (2011).
[2]. Yokoyama, H., Onodera, K., Maeyama, K., et al. Clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, inhibits electrically induced convulsions in mice. Eur. J. Pharmacol. 260(1), 23-28 (1994).
[3]. Dai, H., Fu, Q., Shen, Y., et al. The histamine H3 receptor antagonist clobenpropit enhances GABA release to protect against NMDA-induced excitotoxicity through the cAMP/protein kinase A pathway in cultured cortical neurons. Eur. J. PHarmacol. 563(1-3), 117-123 (2007).