Determination in serum of some barbiturates using micellar liquid chromatography with direct injection.

Elisa Capella-Peiro M, Gil-Agusti M, Martinavarro-Dominguez A, Esteve-Romero J.

Area de Quimica Analitica, Universitat Jaume I, 12080 Castello, Spain.

A procedure was developed for the determination of several barbiturates, amobarbital, barbital, hexobarbital, and secobarbital, using a C18 column (120 x 4.6mm) and micellar liquid chromatography (MLC) mobile phases containing sodium dodecyl sulfate (SDS) and propanol, butanol, or pentanol as a modifier, with UV detection at 230nm. After the application of an interpretative strategy of optimization, the four barbiturates can be resolved and determined in serum samples, allowing the direct injection in 0.10M SDS-4% (v/v) butanol, pH 7, with an analysis time below 8 min. In the proposed MLC procedure, linearities (r >0.999), limits of detection (ngmL(-1)) in the 30-70 range, repeatabilities, and intermediate precision below 1.8% are adequate for the quantification. The proposed method could be applied to the determination of barbiturates in serum samples with recoveries that agreed with the concentration added.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12413460&dopt=Abstract barbiturate Butalbital Fioricet





Barbiturates induce mitochondrial depolarization and potentiate excitotoxic neuronal death.

Anderson CM, Norquist BA, Vesce S, Nicholls DG, Soine WH, Duan S, Swanson RA.

Department of Neurology, University of California, San Francisco, USA.

Barbiturates are widely used as anesthetics, anticonvulsants, and neuroprotective agents. However, barbiturates may also inhibit mitochondrial respiration, and mitochondrial inhibitors are known to potentiate NMDA receptor-mediated neurotoxicity. Here we used rat cortical cultures to examine the effect of barbiturates on neuronal mitochondria and responses to NMDA receptor stimulation. The barbiturates tested, secobarbital, amobarbital, and thiamylal, each potentiated NMDA-induced neuron death at barbiturate concentrations relevant to clinical and experimental use (100-300 microm). By using rhodamine-123 under quenching conditions, barbiturates in this concentration range were shown to depolarize neuronal mitochondria and greatly amplify NMDA-induced mitochondrial depolarization. Barbiturate-induced mitochondrial depolarization was increased by the ATP synthase inhibitor oligomycin, indicating that barbiturates act by inhibiting electron transport sufficiently to cause ATP synthase reversal. Barbiturates similarly amplified the effects of NMDA on cytoplasmic free calcium concentrations. The cell-impermeant barbiturate N-glucoside amobarbital did not influence mitochondrial potential or potentiate NMDA neurotoxicity or calcium responses. However, all of the barbiturates attenuated NMDA-induced calcium elevations and cell death when present at millimolar concentrations. Whole-cell patch-clamp studies showed that these effects may be attributable to actions at the cell membrane, resulting in a block of NMDA-induced current flux at millimolar barbiturate concentrations. Together, these findings reconcile previous reports of opposing effects on barbiturates on NMDA neurotoxicity and show that barbiturate effects on neuronal mitochondria can be functionally significant. Effects of barbiturates on neuronal mitochondria should be considered in experimental and clinical application of these drugs.

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Transient diffuse cerebral hypoperfusion in Tc-99m HMPAO SPECT of the brain during withdrawal syndrome following acute barbiturate poisoning.

Kamijo Y, Soma K, Kondo R, Ohwada T.

Department of Emergency Medicine, Kitasato University School of Medicine, 1-1 5-1 Kitasato, Sagamihara Kanagawa, Japan

A 29-y-old man had taken small daily doses of barbiturates as hypnotics (50 mg pentobarbital, 30 mg phenobarbital) for 4y with no evident intoxication. When he attempted suicide by ingestion of 15 g amobarbital, treatment with charcoal hemoperfusion resulted in rapid disappearance of drug from the blood. Generalized convulsions and delirium ensued; these were responsive to phenobarbital. An electroencephalogram (EEG) showed diffuse 5-Hz theta activity. Tc-99m hexamethylpropyleneamineoxime (HMPAO) single photon emission computed tomographic (SPECT) imaging of the brain demonstrated a diffuse bilateral decrease in blood flow to the cerebral cortex. These investigations were performed interictally on day4 without sedative drugs, prior to initiation of anticonvulsants, and at a time when barbiturates were no longer detected in the serum. An EEG on day 15 no longer showed abnormal slowing. On the other hand, Tc-99m HMPAO SPECT of the brain demonstrated residual cerebral hypoperfusion on day 20, with nearly full recovery of cerebral perfusion on day 51. Barbiturate withdrawal syndrome is presumed to require a history of abuse; however in patients with a history of treatment with barbiturates physicians treating acute barbiturate poisoning should be alert for the possibility of barbiturate withdrawal syndrome even in the absence of barbiturate abuse.

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[Thio- and oxybarbiturates inhibit peristalsis in the Guinea-pig ileum in vitro]

[Article in German]

Herbert MK, Berg W, Kublik A, Holzer P, Roewer N.

Klinik fur Anaesthesiologie der Universitat Wurzburg. mherbert anaesthesie.uni-wuerzburg.de

INTRODUCTION: Inhibition of gastrointestinal motility by drugs used for anaesthesia or sedation in critically ill patients in the ICU is a major problem leading to various complications. Thus this study examines whether the thio- and oxybarbiturates thiopentone and pentobarbitone exert an inhibitory effect on intestinal peristalsis. METHODS: Peristalsis in isolated segments of the guinea-pig small intestine was elicited by distension of the gut wall through a rise of intraluminal pressure and recorded via the intraluminal pressure changes associated with the aborally moving peristaltic contractions. Thiopentone and pentobarbitone (0.1 - 300 microM)-induced inhibition of peristalsis was reflected by an increase of the peristaltic pressure threshold (PPT). RESULTS: Thiopentone (EC50 = 19,8 microM) and pentobarbitone (EC50 = 99.7 micro M) concentration-dependently increased the PPT. While the vehicle (saline) and 0.1 - 10 micro M thiopentone and pentobarbitone were without any effect on the PPT, 100 micro M caused a significant increase in PPT, and complete abolition of peristalsis occurred after 300 micro M thiopentone or pentobarbitone in all segments tested. Inhibition was reversed by changing the bath solution. CONCLUSIONS: Thio- and oxybarbiturates inhibit intestinal peristalsis in the guinea-pig ileum. It is assumed that thiopentone and pentobarbitone affect propulsive peristalsis also in the human small intestine.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12469284&dopt=Abstract barbiturate Butalbital Fioricet