Naloxone displacement at opioid receptor sites measured in vivo in the human brain.
We report the use of a sensitive non-tomographic positron detecting system to measure the dose-response curve of naloxone in human brain. [11C]Diprenorphine was administered to normal volunteers in tracer amounts and, 30 min later, various bolus doses of naloxone were given (1.5-160 microg/kg) intravenously and change in [11C]diprenorphine binding monitored over the next 30 min. We found that this method produced results consistent with existing data. It was observed that approximately 13 microg/kg of naloxone ( approximately 1 mg in an 80 kg man) was required to produce an estimated 50% receptor occupation. This is consistent with the clinical dose of naloxone used to reverse opiate overdose (0.4 mg-1.2 mg).
Melichar
Jan K
JK
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, University Walk, BS8 1TD, Bristol, UK.
Nutt
David J
DJ
Malizia
Andrea L
AL
D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D004174:Diprenorphine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009270:Naloxone / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*
D011957:Receptors, Opioid; D004174:Diprenorphine; D009270:Naloxone