ABSTRACT
Using in vivo microdialysis, a comparative study was conducted to examine the effects of amphetamine-related compounds (methamphetamine, MAP; 3,4-methylenedioxymethamphetamine, MDMA; p-methoxyamphetamine, PMA; p-methoxymethamphetamine, PMMA; 4-methylthioamphetamine, 4-MTA; 3,4,5-trimethoxyamphetamine, TMA; 2,5-dimethoxy-4-iodoamphetamine, DOI) on extracellular levels of serotonin (5-HT) and dopamine (DA). Dialysates were assayed using HPLC equipped with electrochemical detector following i.p. administration with each drug at a dose of 5 mg/kg. MAP was found to drastically and rapidly increase 5-HT and DA levels (870% and 1460%, respectively). PMA, PMMA, and 4-MTA slightly increased DA levels (150-290%) but remarkably increased 5-HT levels (540-900%). In contrast, TMA and DOI caused no detectable changes in levels of both monoamines. We observed that the potent DA-releasing action of MAP was remarkably decreased by introduction of methoxy or methylthio group at the para position (MAP vs. PMMA or 4-MTA), but introduction of two additional adjacent methoxy groups into PMA totally abolished its 5-HT-/DA-releasing action (PMA vs. TMA). In addition, para-mono-substituted compounds inhibited both monoamine oxidase (MAO) enzymes more strongly than other compounds; PMA and 4-MTA exhibited submicromolar IC50 values for MAO-A. On the other hand, TMA scarcely affected the activity of both MAO enzymes as well as extracellular levels of 5-HT and DA. In this comparative study, MDMA, PMA, and 4-MTA functioned similar to PMMA, a typical empathogen; these findings therefore could be helpful in clarifying the psychopharmacological properties of amphetamine-related, empathogenic designer drugs.
Subject(s)
Amphetamines/pharmacology , Brain/drug effects , Brain/metabolism , Central Nervous System Stimulants/pharmacology , Dopamine/metabolism , Serotonin/metabolism , Animals , Chromatography, High Pressure Liquid , Extracellular Fluid/drug effects , Extracellular Fluid/metabolism , Hydroxyindoleacetic Acid/pharmacology , Inhibitory Concentration 50 , Male , Microdialysis , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Rats , Rats, Wistar , Time FactorsABSTRACT
The production of vitamin B12 from carbohydrates, peptone, casamino acid, etc., by intestinal bacteria was investigated. Klebsiella pneumoniae IFO 13541 was the most efficient strain for vitamin B12 production, which depended exclusively on the concentration of yeast extract added to the medium. A concentrated solution of yeast extract (1 ml) was chromatographed on a Sephadex G-25 column (1 x 180 cm) and eluted with H2O (eighty fractions of 3 ml each were collected). It was found that fractions in which bacterial growth was most prevalent also exhibited the highest amount of vitamin production. The effectiveness of yeast extract was shown by the participation of pyrroloquinoline quinone and aspartic acid in the growth stimulation and in the vitamin B12 production in this strain.
