title: Rocastine (AHR-11325), a rapid acting, nonsedating antihistamine.
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 oxatomide. 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 x, 2.63 x, 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 approximately 36 x 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 (150x) of its antihistaminic dose nor did it potentiate yohimbine toxicity in mice. Further, rocastine possesses no anticholinergic, antiadrenergic, or antiserotonergic properties in vitro. Rocastine is a selective, nonsedating, H1-antagonist with a rapid onset of action.
authors.affiliation: Pharmacology Department, A.H. Robins Co., Richmond VA 23261.
authors.forename: J C
authors.initials: JC
authors.lastname: Nolan
authors.forename: D J
authors.initials: DJ
authors.lastname: Stephens
authors.forename: A G
authors.initials: AG
authors.lastname: Proakis
authors.forename: C A
authors.initials: CA
authors.lastname: Leonard
authors.forename: D N
authors.initials: DN
authors.lastname: Johnson
authors.forename: B F
authors.initials: BF
authors.lastname: Kilpatrick
authors.forename: M H
authors.initials: MH
authors.lastname: Foxwell
authors.forename: J M
authors.initials: JM
authors.lastname: Yanni
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D016589:Astemizole; D001381:Azepines / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001977:Brompheniramine / Q000494:pharmacology; D002415:Cats; D002744:Chlorpheniramine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004569:Electroencephalography; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000502:physiology; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D010077:Oxazepines / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology; D011398:Promethazine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D016593:Terfenadine; D015016:Yohimbine / Q000633:toxicity
chemical_list: D001381:Azepines; D001559:Benzhydryl Compounds; D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D010077:Oxazepines; D010879:Piperazines; D015016:Yohimbine; C061192:rocastine; D002744:Chlorpheniramine; D016593:Terfenadine; D016589:Astemizole; D006632:Histamine; D004155:Diphenhydramine; D011398:Promethazine; D001977:Brompheniramine; D011738:Pyrilamine; C015408:oxatomide