Pharmacology & Toxicology
May 1, 1997
Ivone de Souza, John R. Kelly, Andrew Harkin et al.
29 citations
Acute oral administration of MDMA (Ecstasy) to adult female rats produced dose-related effects including hyperthermia, reduced food and water intake, and hyperactivity. Deaths occurred from 40 mg/kg upward. Lower doses (20 and 40 mg/kg) caused prolonged hyperactivity lasting about 9 hours, while higher doses led to serotonin syndrome. The likely cause of death was a combination of serotonin syndrome and hyperthermia.
Pharmacology & Toxicology
June 1, 1999
María Isabel Colado, Raquel Ena María Granados, Esther O’shea et al.
26 citations
A single dose of the recreational drug MDEA ("eve") given to Dark Agouti rats caused an acute, dose-dependent rise in body temperature. The peak hyperthermia from 35 mg/kg of MDEA matched that from 15 mg/kg of MDMA ("ecstasy"). Seven days later, MDMA caused a 50% loss of serotonin and its metabolite in the cortex, hippocampus, and striatum, indicating neurotoxic damage to serotonin nerve endings. MDEA at the highest dose produced only a 20% loss in cortex and hippocampus and no loss in striatum, with weak dose dependence. Neither drug altered striatal dopamine. MDEA had about half the potency of MDMA for hyperthermia and one-quarter the potency for serotonin neuron degeneration.
Pharmacology & Toxicology
January 1, 1987
T Archer
2 citations
Several compounds that block serotonin (5-HT) receptors were tested for their ability to counteract changes in postdecapitation convulsions (PDCs) caused by 5-MeODMT, a serotonin agonist. Mianserin, methergoline, cinanserin, and methysergide substantially reduced the 5-MeODMT-induced prolongation of the time before convulsions began (latency) and, to a lesser extent, the duration of convulsions. Their effectiveness ranked mianserin > cinanserin > methysergide > methergoline. Pirenperone (a 5-HT2 antagonist) and pimozide (a dopamine antagonist) did not block these effects. When given alone, mianserin, methergoline, cinanserin, and methysergide prolonged convulsion duration but not latency; pirenperone prolonged both; pimozide had no effect. This suggests that 5-MeODMT's effects on PDCs are mediated through 5-HT1 receptors, offering a reliable model for studying spinal function.
Pharmacology & Toxicology
May 1, 1999
C Johansson, A M Deveney, D Reif et al.
A selective inhibitor of neuronal nitric oxide synthase, AR-R 17477, counteracts behavioral effects of the psychosis-inducing drug phencyclidine in rats. AR-R 17477 (0.5, 1, and 5 mg/kg) reduced phencyclidine-induced hyperactivity, and 1 mg/kg reversed phencyclidine-induced deficits in prepulse inhibition of the startle response, a measure of sensorimotor gating. Higher doses were less effective. The compound did not alter normal behavior or affect the actions of d-amphetamine. Unlike the non-specific inhibitor L-NAME, AR-R 17477 did not change blood pressure or heart rate. The findings indicate that blocking the neuronal isoform of nitric oxide synthase specifically counteracts phencyclidine's effects, likely without cardiovascular side effects.
Pharmacology & Toxicology
January 1, 1999
G Ellison, A Keys, K Noguchi
Continuous administration of phencyclidine (PCP) to rats over several days causes neural degeneration in limbic brain structures such as the retrosplenial cortex, hippocampus, and piriform cortex. Twenty-one days after the same dosing regimen, autoradiography revealed enduring changes in several receptor types—including decreased binding of TCP, flunitrazepam, and mazindol—in many limbic regions where degeneration had been reported. Unexpectedly, some long-term receptor alterations appeared in structures without immediate signs of degeneration, like the anterior cingulate cortex and caudate nucleus, and some changes developed gradually after drug cessation. These findings do not point to a single source for the neurotoxicity and may inform models of schizophrenia.