Intrapulmonary and intravenous administrations of dihydroergotamine mesylate have similar cardiovascular effects in the conscious dog

Background and purpose: The effects of intrapulmonary artery (i.p.a.) administration of dihydroergotamine mesylate (DHE) were evaluated. Experimental approach: Conscious beagle dogs ( n =4) were given DHE via the i.p.a. or i.v. route as two 0.014 mg kg −1 doses and a 0.14 mg kg −1 dose given 60 min apart. A recovery period of 45 h occurred before crossover to the alternative route. Physiological parameters were monitored by telemetry or direct measurement, and venous blood samples were collected for pharmacokinetic assessments. Key results: No meaningful differences between i.v. and i.p.a. treatments were observed for heart rate, systemic pressures and vascular pressures. Aortic resistance increased 8, 27 and 70%, respectively, following three doses of i.v. DHE compared with 11, 37 and 57%, respectively, with i.p.a. DHE. Carotid artery resistance increased 22, 40 and 87%, respectively, following three doses of i.v. DHE, compared with 17, 45 and 67%, respectively, following i.p.a. DHE. Increases in coronary artery resistance were of similar magnitude following i.v. and i.p.a. DHE administration. Increases in left ventricular systolic and diastolic pressures were seen following all doses of i.v. and i.p.a. DHE. Changes following DHE 0.014 mg kg −1 were minimal and not clinically significant. With DHE 0.14 mg kg −1 by either route, emesis was the most common adverse event. Conclusions and implications: DHE has comparable effects delivered via simulated deep inhalation (i.p.a.) or i.v. administration. The risk of cardiovascular complications is unlikely to be greater following inhalation of DHE. British Journal of Pharmacology (2008) 154 , 1254–1265; doi: 10.1038/bjp.2008.187 ; published online 26 May 2008