Antitussive action of antihistamines is independent of sedative and ventilation activity in the guinea pig.
We studied the oral actions of antihistamines from six chemical classes, namely: the ethanolamines (ENA, diphenhydramine and clemastine); ethylenediamines (EDA, pyrilamine and tripelennamine); piperidines (PPD, terfenadine and astemizole); piperazines (PPZ, hydroxyzine and cetirizine); phenothiazines (PTZ, promethazine), and the alkylamines (ALA, chlorpheniramine and bromopheniramine) on cough reflexes, pentobarbital-induced sedation and minute ventilation in the conscious guinea pig. Antihistamines of the ENA class had minimal effects on capsaicin-induced cough although both diphenhydramine (30 and 100 mg/kg p.o.) and clemastine (30 and 100 mg/kg p.o.) increased sedation time (ST). The PPZ class demonstrated both antitussive and sedating activity. The minimum effective oral antitussive dose (MED) of cetirizine and hydroxyzine was 30 and 10 mg/kg, respectively. The EDA did not exhibit antitussive activity. Tripelennamine (10, 30 and 100 mg/kg p.o.) but not pyrilamine enhanced ST. The MED for the PTZ, promethazine, was 10 mg/kg, and at 100 mg/kg promethazine increased ST. The ALA group displayed antitussive activity but only chlorpheniramine (10 mg/kg p. o.) had any effects on ST. The MED for chlorpheniramine and bromopheniramine was 3 and 10 mg/kg p.o., respectively. The PPD antihistamines, namely terfenadine and astemizole, inhibited cough (MED 30 and 10 mg/kg p.o.) without sedative effects. Of the antihistamines tested only promethazine (100 mg/kg p.o.) depressed ventilation responses; however, this dose of promethazine was associated with adverse behavioral effects. The present findings indicate that the antitussive actions of antihistamines are not directly related to histamine H1-receptor blockade because several antihistamines did not antagonize capsaicin-induced cough. In addition, the antitussive actions of antihistamines are independent of their sedative or ventilation effects.
Schering Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
R L
RL
McLeod
G
G
Mingo
S
S
O'Reilly
L A
LA
Ruck
D C
DC
Bolser
J A
JA
Hey
D000284:Administration, Oral; D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003371:Cough / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology; D005029:Ethylenediamines / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital; D010640:Phenothiazines / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship
D000588:Amines; D000996:Antitussive Agents; D004983:Ethanolamines; D005029:Ethylenediamines; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D010640:Phenothiazines; D010879:Piperazines; D010424:Pentobarbital