Interactions of aminoglutethimide with analgesics using antinociceptive tests in mice

Abstract

The action of aminoglutethimide in alleviating bone pain in women with metastatic breast cancer may be due to either an inherent analgesic effect or an interaction with other analgesic drugs. These possibilities have been investigated in mice by conventional antinociceptive tests. In the abdominal constriction test, aminoglutethimide alone had a dose-related antinociceptive activity. A low dose (which had no pharmacological activity) when co-administered with an effective sub-maximal dose of the analgesic, potentiated the effects of the non-steroidal anti-inflammatory drugs (NSAIDs) tested. In the tail immersion test, aminoglutethimide was inactive and did not enhance the antinociceptive activity of the centrally acting analgesics. As cytochrome P450-dependent routes which are inhibited by aminoglutethimide are not involved in the metabolism of the NSAIDs studied, an interaction at the drug metabolism level cannot explain these results. The NSAID-like activity of aminoglutethimide provides some evidence that the drug's mode of action may involve more than the suppression of oestrogen biosynthesis.