Neurotoxic potential

The stimulation of locomotor activity by MDMA and the importance of mesolimbic dopamine in this response reflect similarities with the prototype phenylethylamine stimulant, amphetamine. It is important to note that these parameters are frequently associated with rewarding aspects of drugs and drug abuse. Additionally, the behavioral profiles of MDMA and I E share certain characteristics with hallucinogen-Iike agents. This unique mixture of stimulus properties and neurochemical actions may contribute to a dangerous behavioral toxicity and neurotoxic potential for drugs like MDMA. 

Stone, D.M. Johnson, M. Hanson, G.R. and Gibb, J.W. A comparison of the neurotoxic potential of methylenedioxy amphetamine (MDA) and its N-methylated and N-ethylated derivatives. Eur J Pharmacol 134 245-248, 1987a. 

Sprague GL, Castles TR, Bickford AA. 1984. Assessment of the delayed neurotoxic potential of isopropyl triphenylphosphate using a nontraditional testing strategy. Toxicol Environ Health 14 773-788. 

In an attempt to find an in vitro assay to predict differences in the neurotoxic potential of bisindole alkaloids, an assay using cultured rat midbrain cells was developed. This system provided a qualitative measure of the effect of compounds on neuronal tissue, and when several compounds (for which clinical toxicity data were available) were evaluated using this method the results were consistent in rank order with the compounds clinical manifestation of neurotoxicity. When vinepidine was studied in this system, it was found to produce a minimal effect (Fig. 7). 

The standard repeated dose toxicity guideline studies include a number of parameters relevant for the evaluation of a substance s neurotoxic potential. In addition to these standard... 

The Neurotoxicity Screening Battery test guideline (OPPTS 870.6200) consists of a functional observational battery, motor activity, and neuropathology. The test battery is not intended to provide a complete evaluation of neurotoxicity, and additional functional and morphological evaluation may be necessary to assess completely the neurotoxic potential of a chemical. 

In general, these occupational exposure studies poorly characterize aluminum exposure. Some of the studies reported aluminum air concentrations for a single time period (Dick et al. 1997 Sim et al. 1997 Sjogren et al. 1996 White et al. 1992), but did not have earlier monitoring data when aluminum exposures were higher. The lack of adequate exposure monitoring data and the different types of aluminum exposure makes it difficult to compare these studies and draw conclusions regarding the neurotoxic potential of inhaled aluminum in workers. 

White Phosphorus Smoke. Information on the neurotoxicity of white phosphorus smoke is limited to an intermediate-duration study that examined the brain for histological lesions (Brown et al. 1981). Inhalation and dermal exposure studies examining a battery of neurological end points (including neurobehavioral effects) would be useful in assessing the neurotoxic potential of white phosphorus smoke. 

Addressing the use of stimulants for the treatment of children, Ellin wood and Tong (1996) concluded, Drug levels in children on a mg/kg basis are sometimes as high as those reported to produce chronic CNS changes in animal studies (p. 14). Juan et al. (1997) warned that when psychostimulants are indicated, as in ADHD, it would seem prudent to prescribe methylphenidate rather than amphetamine, since methylphe-nidate appears to lack the DA [dopamine] neurotoxic potential that has been well documented for amphetamine (p. 174). However, amphetamine has become increasingly popular among clinicians. 

NMDA-Glu-R co-agonist at polyamine site [neurotoxic -potentiates excitotoxicity of NMDA NMDA-R agonists]... 

Spermine (= Gerontine Musculamine Neuridine) (polyamine) All plants NMDA-Glu-R co-agonist, promotes NMDA-R deactivation (polyamine site) (at 1) [neurotoxic -potentiates excitotoxicity of NMDA NMDA-R agonists]... 

A large number of industrial chemicals are hindering children s development, lowering IQ scores, and triggering attention and behavior disorders. The National Institute of Occupational Safety and Health (NIOSH) studies have revealed a large number of chemical substances that cause damage to the human nervous system. The Lancet identified 201 chemicals with the ability to cause neurological effects in humans. Many chemical substances with neurotoxic potential have not been... 

ECETOC. 1992. Evaluation of the neurotoxic potential of chemicals. European Center for Ecotoxicology and Toxicology of Chemicals, Monograph no. 18. Brussels. 

Jiang, G.C., Tidwell, K., McLaughlin, B.A., Cai, J., Gupta, R.C., Milatovic, D., Nass, R., Aschner, M. (2007). Neurotoxic potential of depleted uranium effects in primary cortical neuron cultures and in Caenorhabditis elegans. Toxicol. Set 99 553-65. 

All cells must assemble macromolecular complexes, maintain the intracellular environment, produce energy, and synthesize endogenous molecules in order to survive. Xenobiotics with neurotoxic potential can interfere with key aspects of cellular maintenance including adenosine triphosphate (ATP) synthesis and Ca homeostasis. 

Voltage-gated ion channels are formed by integral membrane proteins that belong to a superfamily of proteins necessary for the formation of channels that are gated (i.e. opened or closed) by changes in membrane potential (Conley and Brammar, 1999). Many xenobiotics with neurotoxic potential interfere with ion channel functions, and they tend to have rapid and sometimes dramatic effects on sensory and neuromuscular functions. 

Many xenobiotics with neurotoxic potential target macro-molecules/processes involved in the metabohsm, release, reuptake, signaUng, storage, synthesis, and transport of neurotransmitters (Cooper et al, 2003). The major neurotransmitter systems are briefly described below. 

Johnson, M.K. (1977). Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Toxicol. 37 113-15. 

Malygin, V.V., Sokolov, V.B., Richardson, R.J., Makhaeva, G.F. (2003). Quantitative structure-activity relationships predict the delayed neurotoxicity potential of a series of O-alkyl-O-methylchloroformimino phenylphosphonates. J. Toxicol. Environ. Health Part A 66 611-25. 

Spencer, P. (1994) Human consumption of plant material with neurotoxic potential. Acta Hort., 375, 341-8. 

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