Central pharmacological activity of a quaternary ammonium compound in streptozotocin diabetic mice.
Possible changes in blood-brain barrier (BBB) function as a result of diabetes were investigated by assessing antagonism of morphine analgesia in diabetic mice by methylnaltrexone (MeNTX), an opioid receptor blocker that does not cross the BBB when administered subcutaneously (SC). In streptozotocin (STZ)-treated diabetic mice--but not vehicle-treated, non-diabetic mice--treatment with SC MeNTX significantly reduced morphine analgesia. In vehicle-treated, non-diabetic mice, morphine analgesia was antagonized by MeNTX administered intracerebroventricularly and by SC naltrexone, which crosses the BBB. Reduction of STZ-induced hyperglycemia by insulin reversed the effectiveness of SC MeNTX in antagonizing morphine analgesia. We hypothesize that in STZ diabetic mice, MeNTX was able to cross the BBB and block brain opioid receptors.
Quock
R M
RM
Department of Basic Sciences, School of Dentistry, Marquette University, Milwaukee, WI 53233.
Ishii
M M
MM
Emmanouil
D E
DE
D000818:Animals; D001812:Blood-Brain Barrier; D002463:Cell Membrane Permeability; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007279:Injections, Subcutaneous; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists; D014677:Pharmaceutical Vehicles; D000644:Quaternary Ammonium Compounds; D013311:Streptozocin
D007328:Insulin; D009292:Narcotic Antagonists; D014677:Pharmaceutical Vehicles; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; D013311:Streptozocin; D009020:Morphine