Rocastine

Rocastine (AHR-11325 ) is an orally active H₁-histamine receptor inhibitor that selectively binds to and functionally inhibits H1-histamine receptors. Rocastine protects guinea pigs from the lethal effect induced by Histamine (HY-B1204), prevents histamine-induced collapse, and protects guinea pigs from the falling reaction induced by nebulized antigens. Rocastine can be used in the research of allergic diseases^[1]. In Vitro:Rocastine binds selectively to H₁-histamine receptors in guinea pig cerebral cortex with an IC₅₀ of 34 nM. It does not bind to α₁-adrenergic receptors, M₁-muscarinic receptors, or 5-HT₂-serotonergic receptors, nor does it interact with H2-histamine receptors in guinea pig mucosa^[1].
Rocastine competitively inhibits histamine-induced contraction of isolated guinea pig ileal strips, with a pA₂ value of 7.67, and shows no anticholinergic activity at concentrations 1000-fold higher than its antihistamine potency^[1]. In Vivo:Rocastine (0.08-6.07 mg/kg; oral gavage; various pretreatment times prior to histamine challenge) is a potent, rapid-acting antihistamine, with oral PD₅₀ values as low as 0.08 mg/kg^[1].
Rocastine (0.46-26.10 mg/kg; oral gavage; 1, 3, or 6 hours prior to histamine challenge) potently protects guinea pigs from histamine-induced prostration, with an oral PD₅₀ of 0.46 mg/kg at 1-hour pretreatment and 2.34 mg/kg at 3-hour pretreatment, demonstrating greater potency than pyrilamine at these time points^[1].
Rocastine (0.316-3.16 mg/kg; oral gavage; 1 hour prior to antigen challenge) potently protects actively sensitized guinea pigs from antigen-induced anaphylactic collapse, with an oral PD₅₀ of 1.00 mg/kg at 1-hour pretreatment^[1].
Rocastine blocks histamine-induced hypotension in cats at intravenous doses starting at 1 mg/kg, and does not induce EEG changes indicative of sedation even at a total cumulative dose of 39.9 mg/kg^[1].
Rocastine does not potentiate yohimbine-induced toxicity in female ICR mice at oral doses of 31.6 mg/kg and 66.0 mg/kg, indicating a lack of CNS depressant activity at these doses^[1].