Pharmacokinetic Approaches to the Study of Drug Action and Toxicity

Ak, Cho; Hiramatsu, Masayuki; Kumagai, Yoshito; Patel, N. K.

doi:10.1037/e495922006-011

Cited by 2 publications

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“…The N-oxidation products do not have direct neurochemical effects, whereas aromatic ring metabolites of Amp release DA (34) and can be retained in the nerve terminal (2). The catechol metabolite of MDMA [(OH) 2 MeAmp] (Figure 1) is toxic to cells, exhibiting catecholaminergic neuronal properties (35), and forms thiol adducts (36).…”

Section: Wwwannualreviewsorg • a Chemical Perspective Of Pharmacolomentioning

confidence: 99%

A Chemical Perspective of Pharmacology and Toxicology

Cho

2018

Annu. Rev. Pharmacol. Toxicol.

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My chemical training provided a somewhat different perspective of biological problems, in the problem itself and approaches to its solution. I was fortunate to have in my laboratory postdocs and students who shared this perspective and used appropriate tools to address problems in amphetamine pharmacology and air pollution toxicology. These apparently disparate areas of research shared two chemical reactions: prooxidant-based generation of reactive oxygen and formation of covalent bonds between electrophiles and biological nucleophiles. This article is an attempt to summarize that research and to identify those individuals who made the contributions.

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Section: Wwwannualreviewsorg • a Chemical Perspective Of Pharmacolomentioning

confidence: 99%

A Chemical Perspective of Pharmacology and Toxicology

Cho

2018

Annu. Rev. Pharmacol. Toxicol.

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The use of toxicokinetics for the safety assessment of drugs acting in the brain

Campbell

1995

Mol Neurobiol

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Pharmacological and toxicological studies undertaken on drugs that affect the brain are frequently performed in disparate species under various experimental conditions, at doses often greatly in excess of those expected to be administered to humans, and the findings are extrapolated implicitly or explicitly with scant regard to differences in the biodisposition of the drugs. Such considerations are necessary since: 1. Species; 2. Strain; 3. Gender; 4. Route; 5. Dose; 6. Frequency and time of administration; 7. Temperature; 8. Coadministration of drugs; and 9. Surgical manipulation are but some of the factors that have been shown to influence the kinetics and metabolism of drugs. This article, using MDMA and other phenylethylamines as examples, provides evidence for the need to measure the exposure of the drugs and their active metabolites in blood and brain (toxicokinetics) in order that conclusions based only on dynamic, biochemical, or histological evidence are more pertinent. Further, the combined use of toxicokinetic-dynamic modeling can lead to a better appreciation of the mechanisms involved and a more useful approach to the calculation of safety margins.

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Pharmacokinetic Approaches to the Study of Drug Action and Toxicity

Cited by 2 publications

References 0 publications

A Chemical Perspective of Pharmacology and Toxicology

A Chemical Perspective of Pharmacology and Toxicology

The use of toxicokinetics for the safety assessment of drugs acting in the brain

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