Determination of the relative involvement of mu-opioid receptors in opioid-induced depression of respiratory rate by use of beta-funaltrexamine.

Using a simple method to measure respiratory rate, it was clearly shown that the depression of respiratory rate caused by morphine, ethylketazocine or [D-Ala2,D-Leu5]enkephalin was not altered by the highly selective, irreversible mu-antagonists, beta-funaltrexamine (beta-FNA) at a dose which produced marked antagonism of morphine antinociception. These results indicated that antinociception and depression of respiratory rate are mediated by different receptor interactions. However using a different method to measure respiratory rate (body plythesmograph), beta-FNA caused substantial antagonism of morphine-induced respiratory depression indicating that the degree to which mu-receptor interactions contribute to the depression of respiratory rate depends on the methodology. Possible explanations for this difference are discussed. It is concluded that careful consideration of the methodology must be given when one measures respiratory rate and caution must be exercised if measurement of rate alone is used to assess opioid-induced respiratory depression.