Agents and Actions

, Volume 28, Issue 1–2, pp 53–61 | Cite as

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

  • J. C. Nolan
  • D. J. Stephens
  • A. G. Proakis
  • C. A. Leonard
  • D. N. Johnson
  • B. F. Kilpatrick
  • M. H. Foxwell
  • J. M. Yanni
Allergy, Histamine and Kinins


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.


Terfenadine Yohimbine Diphenhydramine Astemizole Promethazine 
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Copyright information

© Birkhäuser Verlag 1989

Authors and Affiliations

  • J. C. Nolan
    • 1
  • D. J. Stephens
    • 1
  • A. G. Proakis
    • 1
  • C. A. Leonard
    • 1
  • D. N. Johnson
    • 1
  • B. F. Kilpatrick
    • 1
  • M. H. Foxwell
    • 1
  • J. M. Yanni
    • 1
  1. 1.Pharmacology DepartmentA.H. Robins Co.RichmondUSA

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