Ethanol decreases entry of vincristine into brain of rat: modification by acetylcholine or histamine.
Male Sprague-Dawley rats were anesthetized with pentobarbital sodium and a jugular vein and femoral artery cannulated. Ethanol (3%; 13.3 ml/kg) was injected intraperitoneally 5 min before the administration of 10 microCi [3H]vincristine sulfate intravenously. One minute later, saline, acetylcholine, (1 or 2 micrograms/kg) or histamine (1.25, 2.5 or 5 micrograms/kg) was given intravenously. At 15 min the thoracic cavity was opened, a cardiac sample of blood obtained, and saline infused into the left ventricle to remove blood from the brain. Samples of the cerebral cortex, midbrain, cerebellum, and plasma were subjected to liquid scintillation counting. The concentration of ethanol at 20 min after its administration was 20.3 mg/dl. This was associated with a significant decrease in radioactivity in the cerebral cortex and midbrain and a nonsignificant decrease in the cerebellum. Administration of 2 micrograms/kg of acetylcholine in the presence of ethanol decreased the blood pressure and increased the movement of radioactivity into the cerebral cortex and cerebellum while causing a significant decrease in the midbrain. Histamine (2.5 micrograms/kg) significantly increased the movement into the cerebellum and 5 micrograms/kg decreased the movement into the midbrain. The permeability of the blood-brain barrier to [3H]vincristine was decreased by ethanol and this could be modified regionally by vasoactive doses of acetylcholine and histamine. Possible therapeutic advantage might result if vincristine were given in the presence of ethanol which should diminish the potential neurotoxicity.
Domer
F R
FR
Department of Pharmacology, School of Medicine, Tulane University, New Orleans, Louisiana 70112.
Smith
M E
ME
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D014750:Vincristine / Q000378:metabolism*
D000431:Ethanol; D014750:Vincristine; D006632:Histamine; D000109:Acetylcholine