Neurotoxins/neurotoxicity selectivity

Toxicology. Capsaicin turned out to be an excitatory neurotoxin that selectively destroys afferent nociceptors in vivo and in vitro. It could be proven that it killed cells that express TRPVlAHil (Caterina et al. 1997 and references therein). Capsaicinoids may show acute fatale toxicity when a large dose is given at one time (Suzuki and Iwai 1984 and references therein). Neurotoxicity, cytotoxicity, and genotoxicity have been reviewed recently by Manirakiza et al. (2003). 

The data deseribed above demonstrate that destruction of serotonin axons by MDMA involves the serotonin aetive uptake carrier and that administration of citalopram, a selective serotonin uptake blocker, prior to administration of MDMA, ean prevent the decreases in serotonin markers elicited by MDMA alone. These data are eonsistent with previous reports for other potent serotonin neurotoxins, demonstrating that pretreatment with serotonin uptake blockers can prevent the neurotoxic effects of parachloroamphetamine (Ross 1976 Sanders-Bush and Steranka 1978). Furthermore, it has been shown that MDMA-induced neurotoxicity can be prevented or reversed if a serotonin uptake blocker such as fluoxetine is administered no later than 12 hours after MDMA treatment (Schmidt 1986). 

Neurotoxicity can include effects on behavior and physiology, including motor function, sensory function, and cognitive function. These aspects are mainly studied in safety pharmacology, where the emphases are on functional and behavioral tests (e.g., functional observational battery FOB) (OECD 2004), and neurotoxicity may or may not be associated with changes in neuropathology. Neurotoxins may target different parts of the neuron, and neuronopathies may involve injury to the neurones, followed by necrosis and loss the effects may be broad or selective for a subpopulation of neurons. 

It has been stated that if 6-hydroxydopamine and 6-aminodopamine are to be selective in their neurotoxic behavior the damaging process must occur intraneuronally following uptake and hence concentration of the neurotoxin within the neuron. In vivo electrochemical measurements have shown that about 20% of 6-hydroxydopamine is converted to its p-quinone within a few minutes after injection into rat brain. " The redox equilibrium between 6-hydroxydopamine and its p-quinone or 6-aminodopamine and its p-quinoneimine is apparently maintained by an active redox buffer, probably ascorbate-dehydroascorbate, which exists in brain tissue. The potential of this redox buffer is apparently close to -0.200 V vs. SCE. 

Toxicity The acute toxicity of methyl iodide is moderate by ingestion, inhalation, and skin contact. This substance is readily absorbed through the skin and may cause systemic toxicity as a result. Methyl iodide is moderately irritating upon contact with the skin and eyes. Methyl iodide is an acute neurotoxin. Symptoms of exposure (which may be delayed for several hours) can include nausea, vomiting, diarrhea, drowsiness, slurred speech, visual disturbances, and tremor. Massive overexposure may cause pulmonary edema, convulsions, coma, and death. Chronic exposure to methyl iodide vapor may cause neurotoxic effects such as dizziness, drowsiness, and blurred vision. There is limited evidence for the carcinogenicity of methyl iodide to experimental animals it is not classified as an OSHA "select carcinogen."... 

The reaction schemes shown in Figures 8, 9, 12 and 13 indicate that the oxidation chemistry of 5-HT and 5-HTPP is quite complex. Furthermore, radical intermediates and 4,5-dihydroxytryptamine derivatives are formed under very mild oxidizing conditions and such compounds are either expected to be or indeed are neurotoxic. Of all the other products of oxidation of 5-HT and 5-HTPP which have been thus far isolated only one, 5-hydroxytryptamine-4,7-dione (9), has been tested for its neurotoxic properties and it is clearly the most powerful indolic or catecholamine neurotoxin yet discovered. It does not, however, appear to exhibit any selective toxicity for particular neurons. Nevertheless, it seems probable that many other hydroxylated oxidation products of 5-HT, 5-HTPP and the other 5-hydroxyindoles found in the CNS might be neurotoxic. 

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