Effects of antihistamines and local anesthetics on excess tachycardia in conscious dogs.
Atropine produces cardioacceleration in conscious dogs partly by reversing the pre-existing parasympathetic cardioinhibition and partly by inducing "excess tachycardia" (ET). Because ET occurs independently of adrenergic mechanisms, the present study sought to determine whether ET is generated by a positive chronotropic action of endogenous histamine on pacemaker cell H1 receptors. ET was antagonized in conscious dogs by the H1-receptor antagonists pyrilamine, diphenhydramine, chlorpheniramine and promethazine (1-5 mg/kg i.v.), but not the H2-receptor antagonist cimetidine (2-10 mg/kg i.v.). Pyrilamine (0.1 mg/kg i.v.), but not cimetidine (4 mg/kg i.v.), also eliminated a histamine tachycardia (31 +/- 4.1 beats/min) produced by injecting histamine (22 +/- 14.2 micrograms) into the sinus node artery after pharmacological autonomic blockade. The 30-fold greater dose of pyrilamine required to antagonize ET than histamine tachycardia suggests a nonantihistaminic, and possibly a local anesthetic mechanism of action on ET. Indeed, lidocaine, procaine, propranolol and pyrilamine antagonized ET in doses corresponding to the known relative local anesthetic potencies of these agents. The same doses of pyrilamine, lidocaine and procaine had significantly less effects on a comparable beta adrenergic tachycardia produced by intravenous isoproterenol infusion (0.1-0.5 micrograms/kg/min i.v.) after hexamethonium (10 mg/kg i.v.). The results indicate that H1-receptor blockers antagonize ET because of their local anesthetic effects and not their antihistaminic properties. The results also suggest that the ionic pacemaker mechanisms generating ET and beta adrenergic tachycardia are different.
Rigel
D F
DF
Katona
P G
PG
D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002744:Chlorpheniramine / Q000627:therapeutic use; D004155:Diphenhydramine / Q000627:therapeutic use; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D011343:Procaine / Q000627:therapeutic use; D011398:Promethazine / Q000627:therapeutic use; D011738:Pyrilamine / Q000627:therapeutic use; D013610:Tachycardia / Q000188:drug therapy*
D000779:Anesthetics, Local; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D011343:Procaine; D001285:Atropine; D006632:Histamine; D004155:Diphenhydramine; D008012:Lidocaine; D011398:Promethazine; D011738:Pyrilamine