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Rocastine (AHR-11325), a rapid acting, nonsedating antihistamine

  • Allergy, Histamine and Kinins
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Abstract

Rocastine [AHR-11325, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido-[3,2-f]-1,4-oxazepine-5(4H)-thione (E)-2-butenedioate)] is a rapid-acting, potent, nonsedating antihistamine. In guinea pigs challenged with a lethal dose of histamine, rocastine is as effective [based on 1 hr. oral, protective dose (PD50s)] as brompheniramine, chlorpheniramine, pyrilamine, and promethazine and superior to astemizole, diphenhydramine, terfenadine, and oxaomide. Rocastine has a faster onset of action than does terfenadine; rocastine being as effective with a 15 min pretreatment time (PD50=0.13 mg/kg) as it is with a 1 hr pretreatment time (PD50=0.12 mg/kg), while the 15 min PD50 of terfenadine (PD50=44.0 mg/kg) is 22 times greater than the 1 hr PD50 (PD50=1.93 mg/kg). Against aerosolized histamine, rocastine was 7.12×, 2.63×, and equipotent to pyrilamine in preventing histamine-induced prostration at pretreatment times of 1, 3, and 6 hr, respectively. Rocastine protected guinea pigs from collapse induced by aerosolized antigen; rocastine was ∼36 × more potent (based on 1 hr PD50) than diphenhydramine and as potent as oxatomide and terfenadine. Rocastine did not alter the EEG of cats at doses in vast excess (150×) of its antihistaminic dose nor did it potentiate yohimbine toxicity in mice. Further, rocastine possesses no anticholinergic, antiadrenergic, or antiserotonergic propertiesin vitro. Rocastine is a selective, nonsedating, H1-antagonist with a rapid onset of action.

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  1. Pharmacology Department, A.H. Robins Co., 1211 Sherwood Ave, 23261, Richmond, VA, USA

    J. C. Nolan, D. J. Stephens, A. G. Proakis, C. A. Leonard, D. N. Johnson, B. F. Kilpatrick, M. H. Foxwell & J. M. Yanni

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  2. D. J. Stephens
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  8. J. M. Yanni
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Nolan, J.C., Stephens, D.J., Proakis, A.G. et al. Rocastine (AHR-11325), a rapid acting, nonsedating antihistamine. Agents and Actions 28, 53–61 (1989). https://doi.org/10.1007/BF02022980

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