Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) are structurally similar and represent a serious and growing health threat. Earlier studies in our laboratory have shown that methamphetamine interacts with σ receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and neurotoxicity. However, no research exists which characterizes the interaction between σ receptors and MDMA. Therefore, the goal of the present study was to determine whether σ receptors are involved in the actions of MDMA. In the first part of the study, competition and saturation binding assays were performed to measure the interaction of MDMA with σ receptors. The receptor binding assays revealed that MDMA interacts preferentially with the σ 1 subtype, as compared to the σ 2 subtype, and that this interaction occurs in a competitive manner. The second part of the study focused on behavioral measurements in male, Swiss Webster mice to determine whether a selective σ 1 receptor antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine, 0-30 mg/kg, i.p.) could attenuate the locomotor stimulant actions of MDMA (0-50 mg/kg, i.p.). BD1063 alone had no effect on locomotor activity, but dosedependently attenuated the locomotor stimulant effects of (+)-MDMA and produced a significant shift to the right in the MDMA dose response curve. Together, the data support the functional relevance of the interaction of MDMA with σ 1 receptors, and suggest that these receptors are involved in the stimulant actions of MDMA.

Doripenem 5 mg/mL in 5% dextrose injection or in 0.9% sodium chloride injection was physically compatible for four hours at room temperature with 75 drugs during simulated Y-site administration. Three drugs combined with doripenem in 5% dextrose injection or 0.9% sodium chloride injection and 7 drugs combined with doripenem in 0.9% sodium chloride injection resulted in unacceptable precipitation or an increase in measured haze and should not be simultaneously administered with doripenem admixtures.