Influence of different routes of administration on the cardiovascular effects of dihydrexidine (DHX) in rats

T. H. Wu, K. W. Locke, S. B. Loar, T. J. Maher

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摘要

The intranasal (IN) route of administration may provide more rapid and complete delivery of various pharmacological agents to the CNS, while minimizing the peripherally-mediated non-therapeutic actions of such agents. We demonstrated previously that IN administration of the dopaminergic agonist DHX produced robust contralateral turning behavior in a 6-hydroxydopamine unilateral striatal lesioned rat model. Here, we evaluate the hypotensive side effects of DHX administered IN or IV. Male Sprague-Dawley rats were anesthetized with urethane and the right carotid artery and left jugular vein cannulated for mean arterial pressure (MAP) measurement and IV drug delivery, respectively. Rats then received either IN or IV DHX or vehicle. The peak changes in MAP following 0.5, 1.0, 2.0 and 6.0 mg/kg of IN DHX were -5 ± 2, -6 ± 3, -12 ± 3 and -7 ± 3 mmHg, respectively, while following 0.25, 0.5, 0.75 mg/kg of IV DHX peak MAP changes were -22 ± 2, -25 ± 3, -28 ± 3 mmHg, respectively. The IN doses of DHX used, while previously shown to produce robust CNS effects, produced significantly less unwanted cardiovascular effects compared with the IV route. The potential utility of IN DHX should be further explored in human disorders that benefit from CNS dopaminergic stimulation such as Parkinson's disease.

原文英語
期刊FASEB Journal
12
發行號5
出版狀態已發佈 - 三月 20 1998
對外發佈

ASJC Scopus subject areas

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學

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