Neurotoxic effects of the alpha-ethyl homologue of MDMA following subacute administration.
The possible neurotoxic effects of the alpha-ethyl homologue of MDMA, N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), were examined following a regimen of twice daily dosing for four days. The levels of norepinephrine, serotonin and its metabolite 5-HIAA were quantitated by standard HPLC-EC techniques. In addition, the number of 5-HT uptake sites was estimated by examining the binding of [3H]-paroxetine to rat cortex homogenate. With 20 mg/kg (IP) subacute dosing of MDMA, a nearly 60% reduction in 5-HT, 5-HIAA, and 5-HT uptake sites was found, with no change in NE, two weeks posttreatment. A behaviorally equipotent dose of MBDB (25 mg/kg, IP) also produced a significant decrease in the serotonergic markers; 5-HT, 5-HIAA and [3H]-paroxetine binding sites. However, a comparison of the relative toxic effects of MDMA and MBDB indicates that MBDB may be slightly less neurotoxic. It was also found that MDMA but not MBDB caused a significant increase in dopamine levels at 3 hours following a single IP injection. The results are discussed in relation to the therapeutic index of MBDB and the relative importance of dopamine release in the neurotoxicity of MDMA.
Johnson
M P
MP
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Nichols
D E
DE
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity*; D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D000662:Amphetamines; D015306:Biogenic Monoamines; D010880:Piperidines; C051570:N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; D012701:Serotonin; D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine