[The usefulness of a model of acute hypoxia for the testing of cerebroprotective drugs].

Abstract

The aim of this study was to find out whether the mouse in acute normobaric hypoxia (3.5% O2) may be appropriate as a screening model for testing cerebroprotective drugs. The survival time of the mice in hypoxia was used to determine drug effects. 39 agents with various pharmacological and toxicological properties were investigated. Cerebroprotective, centrally depressant and stimulating as well as cardiovascular drugs were included. Only 6 out of 16 cerebroprotective drugs used therapeutically prolonged the survival time of mice in acute hypoxia. However, a positive effect was demonstrable especially for those cerebroprotective drugs (extractum Ginkgo bilobae, meclofenoxate, naftidrofuryl, pentoxifylline and pyritinol), which are generally accepted to be active. On the other hand, 12 out of 23 drugs which are therapeutically used as cardiovascular drugs, central stimulants or depressants or have known toxicological effects also prolonged the survival time of mice in hypoxia. Thus, it became clear that the result of this hypoxia test may be influenced by various pharmacological actions. Especially drugs stimulating the cardiovascular system or depressing CNS activity could prolong the survival time of mice in hypoxia, whereas drugs with vasodilating effects could even shorten it. Opposite effects could superpose or neutralize each other. Therefore, the mouse in acute hypoxia seems to be of limited value as a screening model for testing cerebroprotective drugs.

• Authors: J Krieglstein, H Heuer
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 36 Issue 11 Pg. 1568-71 (Nov 1986) ISSN: 0004-4172 [Print] Germany
• Vernacular Title: Uber die Brauchbarkeit eines Modells der akuten Hypoxie zur Testung zerebroprotektiver Pharmaka.
• PMID: 3814218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Cerebrovascular Circulation (drug effects)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Hemodynamics (drug effects)
• Hypoxia (physiopathology)
• Male
• Mice