Quaternary opiate antagonists lower blood pressure and inhibit leucine-enkephalin responses.

The quaternary opiate antagonists naloxone methylbromide (MB) and naltrexone MB do not cross the blood-brain barrier, and may be used to differentiate peripheral from central nervous system effects of the opioid peptides. When administered intravenously to the conscious, chronically instrumented dog, naloxone MB transiently reduces mean systemic arterial pressure and increases heart rate in a dose-dependent manner over the concentration range from 0.1 to 1.0 mg/kg. The [Leu5]enkephalin response is completely inhibited at naloxone MB doses as low as 0.25 mg/kg, but this inhibition has terminated by 30 min after dosing. Naltrexone MB displays a similar spectrum of activity. This inhibition of the intravenous [Leu5]enkephalin response by the quaternary opiate antagonists indicates that the [Leu5]enkephalin response occurs by activation of peripheral receptor sites. The decrease in mean pressure induced by these antagonists coupled with the inhibition of the [Leu5]enkephalin response suggests that peripheral enkephalins may play a role in blood pressure regulation.