No abstract

1 We investigated whether dopamine plays a role in the neurodegeneration of 5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after 3,4-methylenedioxymethamphetamine (MDMA or`ecstasy') administration. 2 Haloperidol (2 mg kg 71 i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg 71 i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA+haloperidol treated rats was kept elevated, this protective e ect was marginal. 3 MDMA (15 mg kg 71 ) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg 71 i.p., plus benserazide, 6.25 mg kg 71 i.p.) injected 2 h after MDMA (15 mg kg 71 ) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L-DOPA (25 mg kg 71 ) injected before a sub-toxic dose of MDMA (5 mg kg 71 ) failed to induce neurodegeneration. 4 The MDMA-induced increase in free radical formation in the hippocampus (indicated by increased 2,3-and 2,5-dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L-DOPA. 5 The neuroprotective drug clomethiazole (50 mg kg 71 i.p.) did not in¯uence the MDMA-induced increase in extracellular dopamine. 6 These data suggest that previous observations on the protective e ect of haloperidol and potentiating e ect of L-DOPA on MDMA-induced neurodegeneration may have resulted from e ects on MDMA-induced hyperthermia. 7 The increased extracellular dopamine concentration following MDMA may result from e ects of MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than aǹ amphetamine-like' action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings.

Terminally ill cancer patients commonly suffer from several symptoms at the same time, such as pain, nausea, anxiety, cognitive failure, bowel obstruction, and fatigue. To obtain optimal symptom control, the simultaneous administration of more than one drug by continuous subcutaneous (SC) infusion is often required. Tramadol is considered an effective step II agent of the World Health Organization's analgesic ladder for the control of chronic pain conditions, including neuropathic pain, and also exhibits a good safety profile. Haloperidol has been found to be very efficient in controlling agitation with or without pain, nausea and/or vomiting of central origin, intestinal obstruction, and delirium. Although the combination of tramadol and haloperidol in the same solution for SC infusion may be desirable, the physicochemical stability of this combination has not yet been documented. Therefore, our aim was to study the physicochemical stability of drug admixtures composed of tramadol hydrochloride and haloperidol lactate, which have been stored in polypropylene syringes at 4 degrees C and 25 degrees C, and assayed at 0, 5, 7, and 15 days after preparation.