Differential effects of ibogaine pretreatment on brain levels of morphine and (+)-amphetamine.
Previous studies in rats have shown that ibogaine inhibits neurochemical and behavioral effects of morphine yet potentiates similar effects of (+)-amphetamine. To assess whether these different functional interactions have a metabolic basis, brain levels of morphine and (+)-amphetamine were measured by gas chromatography-mass spectrometry after ibogaine pretreatment (19 h before injection of morphine or (+)-amphetamine). Ibogaine pretreatment had no effect on brain morphine levels, either at 30 min or 2 h after morphine injection; however, ibogaine significantly increased brain amphetamine levels at 30 min and, to a greater extent, at 2 h after (+)-amphetamine injection. These and other data suggest that ibogaine irreversibly inhibits an amphetamine-metabolizing enzyme. The functional interactions between ibogaine and (+)-amphetamine, but not those between ibogaine and morphine, may result from a hepatic drug-drug interaction.
Glick
S D
SD
Department of Pharmacology and Toxicology, Albany Medical College, NY 122208.
Gallagher
C A
CA
Hough
L B
LB
Rossman
K L
KL
Maisonneuve
I M
IM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007050:Ibogaine / Q000494:pharmacology*; D009020:Morphine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007050:Ibogaine; D009020:Morphine; D003913:Dextroamphetamine