Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception.
The goal of this study was to evaluate the effects of intranasally administered opioids in rhesus monkeys using the tail-withdrawal assay, and to correlate these effects with measures of receptor occupancy using positron emission tomography (PET) imaging. Initial experiments characterized the antinociceptive effects of intranasal (IN) fentanyl and buprenorphine relative to intramuscular (IM) injection. Fentanyl (0.010-0.032 mg/kg) and buprenorphine (0.1-1.0 mg/kg) produced dose-dependent increases in tail-withdrawal latency that did not differ between routes of delivery. The second experiment compared the ability of IN and intravenous (IV) naloxone (NLX) to block the antinociceptive effects IV fentanyl, and to measure receptor occupancy at equipotent doses of NLX using PET imaging. IN and IV NLX (0.0032-0.032 mg/kg) produced dose-dependent decreases in fentanyl-induced antinociception. Again, there was no difference observed in overall potency between routes. PET imaging showed that IV and IN NLX produced similar decreases in receptor occupancy as measured by [11C]carfentanil blocking, although there was a trend for IV NLX to produce marginally greater occupancy changes. This study validated the first procedures to evaluate the IN effects of opioids in rhesus monkeys.
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan acconep@umich.edu.
Phillip A
PA
Saccone
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Angela M
AM
Lindsey
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Robert A
RA
Koeppe
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Kathy A
KA
Zelenock
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Xia
X
Shao
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Phillip
P
Sherman
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Carole A
CA
Quesada
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
James H
JH
Woods
Department of Pharmacology (P.A.S., A.M.L., K.A.Z., J.H.W.) and Department of Radiology (R.A.K., X.S., P.S., C.A.Q., P.J.H.S.) University of Michigan Medical School, Ann Arbor, Michigan.
Peter J H
PJ
Scott
D000281:Administration, Intranasal; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects*; D049268:Positron-Emission Tomography
D000701:Analgesics, Opioid; D009270:Naloxone; D005283:Fentanyl