Psychopharmacology
January 1, 1991
C W Callaway, M P Johnson, L H Gold et al.
70 citations
MBDB, a derivative of amphetamine that releases little or no dopamine, caused rats to become hyperactive and suppressed their exploratory behaviors, similar to the effects of MDMA. This hyperactivity lasted over 60 minutes at higher doses. Pretreatment with fluoxetine, a serotonin reuptake inhibitor, blocked MBDB-induced hyperactivity, indicating that the behavioral effects depend on serotonin release rather than dopamine release. Fluoxetine also blocked hyperactivity from related drugs S-(+)3,4-methylenedioxyamphetamine and p-chloroamphetamine. Tissue measurements showed decreased serotonin and its metabolite 5-HIAA after MBDB or S-(+)MDMA, which was prevented by fluoxetine. S-(+)MDMA increased dopamine levels in a fluoxetine-sensitive manner, suggesting serotonin release may indirectly influence dopamine.
Pharmacology, biochemistry, and behavior
January 1, 1990
M P Johnson, C A Mathis, A T Shulgin et al.
56 citations
A radiolabeled compound, [125I]-2C-I, was used to label low-density 5-HT2 agonist binding sites in brain tissue. The nonhydrolyzable GTP analog GppNHp inhibited high-affinity binding, and serotonin along with several 5-HT2 agonists and antagonists showed high affinity for the site. At 37°C, the number of binding sites (Bmax) decreased compared to 24°C, while binding affinity (KD) remained unchanged. Structure-activity relationships for displacing [125I]-2C-I supported the receptor's role in hallucinogen action. The findings demonstrate [125I]-2C-I as a useful radioligand and provide further evidence linking the 5-HT2 receptor to hallucinogenic activity.
Pharmacology, biochemistry, and behavior
May 1, 1989
M P Johnson, D E Nichols
26 citations
A behaviorally equipotent dose of the MDMA analogue MBDB (25 mg/kg) produced significant decreases in serotonin, its metabolite 5-HIAA, and serotonin uptake sites in rat cortex, similar to the nearly 60% reductions caused by MDMA (20 mg/kg) two weeks after treatment. However, MBDB appeared slightly less neurotoxic than MDMA. Unlike MDMA, MBDB did not cause a significant increase in dopamine levels three hours after a single injection. The findings suggest that dopamine release may play a role in MDMA's neurotoxicity.