Determination of phenothiazine compounds in biologic specimens by UV spectrophotometry.
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An approach is described for estimating the dose of a new drug which is equipotent to an established dose of an old drug. The approach is basically that of the parallel-line assay but it can allow for concomitant variables and, by exploiting the facilities available in the statistical computer package GLIM (generalized linear interactive modelling), the approach can be applied when the residuals conform to one of a number of distributions and, with suitable safeguards, to continuous, discrete and even 'scored' responses. In some circumstances, it is necessary to obtain confidence limits by Efron's 'bootstrap' technique. The method is illustrated with results from a trial of two premedicant drugs in children.
Survival studies on irradiated euoxic E. coli B/r cells in presence of various concentrations of four radioprotecting phenothiazine drugs have been carried out. Maximum radioprotection was obtained at a optimal concentration for each drug and it decreased on either side of it. The DNA strand break studies at the maximum protective and non-protective concentrations of chlorpromazine and promethazine revealed that the number of ssbs in DNA were less at the protective concentration which were efficiently repaired by the type-III repair process. On the other hand, at the non-protective concentrations, inhibition of DNA repair was noticed and a higher number of DNA ssbs were detected. We suggest that the membrane is fluidized to a greater extent at the protective concentrations allowing the chemical restitution of damaged sites by NPSH compounds. At the non-protective high concentrations of the drugs, the membrane may be too grossly disorganised to allow any repair and at the same time high concentrations of the drugs or their radicals may also react with radioprotective intracellular sulphhydryls.
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UNLABELLED: Neuroleptic malignant syndrome (NMS) is a rare but serious disorder caused by antipsychotic medication including phenothiazines. For sedative purposes, increasing doses of alimemazine were administered to a 4-year-old multiple handicapped girl, with cerebral damage of the basal ganglia. She developed extra-pyramidal motor disturbances, an autonomic disorder, lowered consciousness and hyperthermia, characterising NMS. Alimemazine was stopped and dantrolene and supportive measures, including ventilation under sedation and paralysis with midazolam and vecuronium, were started. As clinical symptoms remained unabated, increasing doses of bromocriptine were administered. Two days after maximal bromocriptine dosage, her clinical condition improved and paralysis and ventilation were stopped. Midazolam and bromocriptine could be gradually decreased and suspended during the following months. A few days after bromocriptine cessation NMS recurred and was complicated by a fatal cardiorespiratory arrest. CONCLUSION: caution must be exercised when prescribing alimemazine, especially to children with basal ganglia damage and in the case of inexplicable fever and restlessness, neuroleptic malignant syndrome should be considered. Long-term therapy with bromocriptine combined with dantrolene and midazolam may be a successful medical treatment.
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