Tenuate online research references
Ann N Y Acad Sci. 2002 Jun;965:214-24.
Neurotoxicity of diethylpropion: neurochemical and behavioral findings in rats.
Galvan-Arzate S, Santamaria A.
Departamento de Neuroquimica, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, S.S.A. Mexico D.F. 14269, Mexico.
The effects of diethylpropion (DEP), an amphetamine derivative and a well-known anorectic agent, on different neurochemical and behavioral markers of toxicity in rats were evaluated. Animals received a daily dose of DEP (5 mg/kg po) for 15 days, and all tests were performed 24 hours after the last DEP administration. As neurochemical markers, the brain regional levels of some amino acids, such as aspartate (Asp), glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln), as well as the brain regional rates of lipid peroxidation as a current index of oxidative stress were measured. As behavioral markers, the actions of DEP on both mercaptopropionic acid (MPA)-induced seizures and kainic acid (KA)-induced wet-dog body shakes were explored to investigate whether DEP induces behavioral sensitization to the effects of agents affecting the central activity of neuroactive amino acids. Treatment with DEP produced significant changes in the levels of Asp in the hypothalamus (Ht) and cortex (Cx); Glu in the Ht, Cx, midbrain (Mb), and striatum (S); and Gln in the Cx. The regional levels of GABA remain unchanged. Lipid peroxidation was increased in the hippocampus (Hc), Mb, and S. Also, latency to the first seizure induced by MPA (1.2 mmol/kg i.p.) and the total number of wet-dog body shakes induced by KA (10 mg/kg i.p.) were significantly affected by DEP treatment. These findings suggest that low doses of DEP may affect different neurochemical substrates, inducing changes in neuroactive amino acids along the brain regions, probably involving dopamine release. Consequently, behavioral changes could be the result of excitotoxic events related to excessive Glu or lack of an inhibitory process. Also, DEP is thought to involve free radical formation and oxidative stress as potential features of its regional pattern of neurotoxicity, as evidenced by lipid peroxidation.
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Drug Metab Rev. 1975;4(2):267-76.
The objective and timing of drug disposition studies, appendix III. Diethylpropion and its metabolites in the blood plasma of the human after subcutaneous and oral administration.
Wright GJ, Lang JF, Lemieux RE, Goodfriend MJ Jr.
Diethylpropion hydrochloride is an effective anorexiant at the recommended dose of 25 mg three times a day. Previous work in volunteers to evaluate the effects of much larger doses showed that 400 mg given orally was equipotent with 600 mg subcutaneously in terms of subjective and physiologic effects, i.e., the drug was more potent orally than subcutaneously. In one volunteer, blood level studies after a 600-mg subcutaneous dose showed concentrations of unchanged diethylpropion in the plasma about three times as high as those found after the equipotent 400 mg oral dose. In nine other volunteers, the plasma concentrations of unchanged diethylpropion found after a 75-mg oral dose was less than 1/100 of that observed after a 400-mg oral dose. These observations suggest a rapid but limited metabolic capacity for conversion of diethylpropion to its metabolites. The data indicate that the metabolites, rather than the parent drug, are responsible for the pharmacologic responses seen with doses much larger than those necessary for inducting anorexia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1222683&dopt=Abstract
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