Biological convulsant response

Nobler MS, Sackeim HA Augmentation strategies in electroconvulsive therapy a synthesis. Convulsive Therapy 9 331-351, 1993 Nobler MS, Sackeim HA Electroconvulsive therapy clinical and biological aspects, in Prediction of Treatment Response in Mood Disorders. Edited by Goodnick P. Washington, DC, American Psychiatric Press, 1996, pp 177-198 Nobler MS, Sackeim HA, Solomou M, et al EEG manifestations during ECT effects of electrode placement and stimulus intensity. Biol Psychiatry 34 321-330, 1993 Nobler MS, Sackeim HA, Prohovnik 1, et al Regional cerebral blood flow in mood disorders. III treatment and clinical response. Arch Gen Psychiatry 51 884-897, 1994... 

Neurological Effects. Little information was available to determine the neurotoxicity or the mechanism of neurotoxicity of HDI after inhalation, oral, or dermal exposure. Headache was reported in only one human exposure case (Malo et al. 1983). Neurotoxic effects (convulsions) may occur in laboratory animals if concentrations reaeh high levels in the air (Haskell Laboratory 1961) however, sinee HDI is metabolized quickly in a biological matrix (Berode et al. 1991), little intaet HDI is expected to reach the nervous tissue to elicit a toxic response, except possibly at very high eoneentrations. No neurological effects have reported in laboratory animals, or in hiunans exposed chronieally to low concentrations of HDI (Mobay Corporation 1989). HDI, in addition to other isocyanates, have been shown to inhibit acetylcholinesterase in human erythrocytes (Dewair et al. 1983), human serum acetylcholinesterase (Brown et al. 1982), as well as equine serum, bovine erythrocyte, and eel acetylcholinesterase (Brown et al. 1982). 

Malathion is an example of an organophosphorus insecticide, which works by inhibition of the enzyme acetylcholinesterase, responsible for the hydrolysis of the neurotransmitter acetylcholine. Inhibition of the enzyme allows the build-up of lethal concentrations of acetylcholine, convulsions and death. Malathion is a weak inhibitor of the enzyme and in humans is hydrolysed to the corresponding acid, which also has a low biological activity. In insects, malathion is oxidised to malaoxon which is 10 000 times more active than the parent compound. This causes an increase in levels of acetylcholine, which kills the insect (see Figure 5.10). 

Several substituent constants, including the Taft Eg, have been employed by Hamor and Lien in the study of anticonvulsant activities of alkyl esters of 2-sul amoylbenzoic acid against maximal electroshock and against strychnine-induced convulsions. The steric substituent constant, E, the electronic substituent constants, a and o, ana log P calculated from Hansch s ir values were examined for correlation with biological response. For antistrychnine action, the best... 

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