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PubMedDate not supplied

Overpressured layer chromatographic study of retention behaviour of various benzodiazepine derivatives on layers impregnated with tricaprylmethylammonium chloride.

The retention behaviour of various benzodiazepine derivatives was investigated on silica gel layers impregnated with tricaprylmethylammonium chloride (TCMA). The chromatograms were developed by means of overpressured layer chromatography (OPLC). As for the case of amino- and nitrosalicylic acids, pyrimidine derivatives, barbiturates, penicillins, cephalosporins and tetracyclines, the retention of benzodiazepine derivatives increased with increasing layer TCMA concentration with eluents containing methanol and water, but not TCMA. On increase of the methanol content of the eluent, a retention-decreasing effect was observed. On layers impregnated with TCMA, a linear relationship existed between the RM values of the benzodiazepines and the methanol content of the eluent. A similar relationship held for silica gel layers impregnated with paraffin oil (traditional reversed-phase). There was no correlation between the results obtained on layers treated with TCMA or with paraffin oil. On TCMA-impregnated layers, the retention of compounds having different chemical structures showed no dependence on the pH of the eluent. There were two reasons for this. Firstly, as it was established, above a certain RF value, the pH of the layer in the presence of TCMA was almost identical irrespective of the original pH of the buffer. Secondly, below this RF value, the actual pH of the layer did not have a strong enough effect to cause appreciable differences between the retentions of the dissociated and undissociated species of the analytes. The conditions for optimum separation are given.

Anti-Anxiety Agents↗
PubMedDate not supplied

Factors influencing serum levels of carbamazepine and carbamazepine-10,11-epoxide in children.

Carbamazepine-10,11-epoxide (CBZ-E), the principal metabolite of carbamazepine (CBZ), is reported to have antiepileptic and toxic effects similar to CBZ. Steady-state CBZ and CBZ-E levels (high performance liquid chromatography, HPLC assay) were reviewed in 225 outpatient children and young adults taking CBZ with or without other antiepileptic drugs (AEDs). In patients on CBZ alone, mean serum concentration of CBZ was 7.9 +/- 1.9 micrograms/ml and of CBZ-E was 1.5 +/- 0.6 micrograms/ml. The CBZ-E/CBZ ratio was 19.6 +/- 2.4%. Serum CBZ increased with increasing age and with CBZ dose. CBZ-E increased with increasing CBZ dose but was unaffected by age. The CBZ-E/CBZ ratio progressively declined with age. Co-medication with barbiturates or valproic acid significantly increased CBZ-E. Phenytoin showed a similar trend while ethosuximide caused the least change. Patients on CBZ and two or more other AEDs had highest CBZ-E levels and CBZ-E/CBZ ratio. CBZ and CBZ-E levels are variably affected by age, CBZ dose, and co-medication with other AEDs. When other AEDs are administered, careful monitoring is especially indicated in order to avoid toxicity.

Adolescent↗
PubMed1976

Synthesis and neuropharmacology of cyclobutanecarboxylic acid derivatives.

Urea, hydrazide and amide derivatives of cyclobutanecarboxylic acid have been examined for central nervous systems depressant properties, potentiation of barbiturate induced sleep, myorelaxant, antitremorine and anticonvulsant activity. The urea derivatives have central nervous system depressant qualities while the hydrazines and heterocyclic amides are either inactive or have central nervous system excitatory properties. N,N'-o-methoxybenzylidenebiscyclobutanecarboxamide and 1,3-dicyclo-butanecarbonyl-2-thiourea are myorelaxant; 1-cyclobutanecarbonyl-3-allylurea antagonizes Metrazol induced convulsions; 1,3-dicyclobutanecarbonyl-2-thiourea and N-cyclobutanecarbonyl morpholine antagonizes tremorine induced tremors.

Animals↗
PubMed1979

Detection of drugs using XAD-2 resin. II:Analysis of liver in medical examiner's cases.

Liver tends to concentrate drugs in quantities generally higher than those found in blood or other body compartments. This fact as well as the general availability of liver in postmortem cases makes it an important specimen for comprehensive toxicologic investigation. A scheme for the analysis of liver for drugs with tissue hydrolysis, XAD-2 resin extraction, and TLC has been developed and the parameters affecting recovery have been studied. The hydrolysis of liver specimens at various pH conditions resulted in an improved recovery for morphine by using pH 2 (2N hydrochloric acid). Recoveries of barbiturates, codeine, and meperidine were essentially the same at pH 2 and pH 3. A considerable loss (22 to 55%) was observed for four drugs (pentobarbital, morphine, codeine, and meperidine) as a result of drug binding to the tissue pellets during the process of centrifuging the liver homogenates. This method is recommended as a comprehensive screening procedure for drugs in liver tissue. For quantitative purposes, however, it is necessary to determine a correction factor for all the losses occurring at the various steps of the procedure. This procedure compared favorably with other procedures for liver analysis reported in literature.

Barbiturates↗
PubMed1996

A comparative review of the adverse effects of anticonvulsants in children with epilepsy.

Phenobarbital (phenobarbitone) and phenytoin are the most useful anticonvulsants in neonates because adverse effects are most readily reversed when these drugs are used. Most anticonvulsants are very rarely associated with haematological adverse effects. Platelet function is particularly vulnerable to valproic acid (sodium valproate) therapy. Barbiturates and phenytoin can precipitate metabolic bone disease. Although very infrequent, lymphadenopathy is most common with phenytoin, and lupus-like illnesses with ethosuximide. Valproic acid may precipitate underlying metabolic disorders. Nephrolithiasis can occur with topiramate. Liver disease is most likely with felbamate or valproic acid, but can occur with other anticonvulsants. Valproic acid and ethosuximide are the main precipitants of gastrointestinal symptomatology; while valproic acid and vigabatrin are frequently associated with excessive bodyweight gain. Rash is most likely to occur with barbiturates, but there is a high risk of this adverse effect if large doses of lamotrigine are given with valproic acid. Adverse cosmetic effects are most likely with phenytoin, but valproic acid may cause alopecia. All anticonvulsants may cause unwanted neurological effects: when they occur, diplopia is usually precipitated by carbamazepine; tremor by valproic acid; and other motor disturbances are probably most common with phenytoin. Most anticonvulsants can cause drowsiness. Phenobarbital leads anticonvulsants as a cause of behavioural difficulties. Effects of anticonvulsants on cognitive function are difficult to assess, but subtle changes have been reported for all anticonvulsants in use up to the 1980s. Compared with other anticonvulsant drugs, phenytoin and felbamate are more often discontinued as a result of unwanted effects.

Adolescent↗
PubMed1988

Depolarizing actions of convulsant barbiturates on isolated rat dorsal root ganglion cells.

The actions of convulsant barbiturates were studied on dorsal root ganglion (DRG) cells in vitro using intracellular recording techniques. Only the convulsant barbiturates (+)-DMBB and CHEB produced a concentration-dependent depression in the responses to gamma-aminobutyric acid (GABA). All convulsant barbiturates were found to produce a direct depolarization of the DRG cell membrane which was accompanied by a decrease in the input resistance of the cell and a reduction in the orthodromic action potential. A sub-population of DRG cells were found to be refractory to these actions but there was no relationship between the cell type (A beta, A delta and C) and ability to respond to the convulsant barbiturates.

Animals↗