Response map properties of units in the dorsal cochlear nucleus of barbiturate-anesthetized gerbil (Meriones unguiculatus).

Gdowski GT, Voigt HF.

Department of Biomedical Engineering, Boston University, MA 02215-2407, USA.

The response map scheme introduced by Evans and Nelson (1973) and modified by others, including Davis et al. (1996) for use with gerbils, has been used primarily for classifying units recorded in the cochlear nucleus of unanesthetized decerebrate preparations. Units lacking spontaneous activity (SpAc) have been classified as either type I/III or type II units based on the relative strength of their responses to broad-band noise compared to their responses to best-frequency (BF) tones. The relative noise index (rho), a ratio of these responses after SpAc is subtracted out, provides a convenient measure of this relative strength. In this paper, responses of 320 units recorded in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized gerbils to short-duration BF tones and broad-band noise were recorded. Since 87.5% of these units lacked SpAc, their response maps resembled those of type II and type I/III units. Units were characterized by rho and the normalized slope (m) of a best line fit to the BF rate versus level plot starting from the sound level corresponding to the first inflection point of the rate curve (typically its maximum value or the start of its sloping saturation). The distributions of rho and m values do not form distinct clusters as they do for units in the decerebrate preparation. Thus, the criteria developed for classifying DCN units in the decerebrate preparation do not appear appropriate for units in the barbiturate-anesthetized preparation. Deposits of horseradish peroxidase were used to locate 52 units. Most of the low SpAc units, 56% with poor noise responses (5/9) and nearly 70% with strong noise responses (25/36), and nearly all of the high SpAc units (6/7), were located either within or below the fusiform cell layer.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9083807&dopt=Abstract barbiturate Butalbital Fioricet





Mechanisms of barbiturate inhibition of acetylcholine receptor channels.

Dilger JP, Boguslavsky R, Barann M, Katz T, Vidal AM.

Department of Anesthesiology, University at Stony Brook, New York 11794-8480, USA. dilger ccmail.sunysb.edu

We used patch clamp techniques to study the inhibitory effects of pentobarbital and barbital on nicotinic acetylcholine receptor channels from BC3H-1 cells. Single channel recording from outside-out patches reveals that both drugs cause acetylcholine-activated channel events to occur in bursts. The mean duration of gaps within bursts in 2 ms for 0.1 mM pentobarbital and 0.05 ms for 1 mM barbital. In addition, 1 mM barbital reduces the apparent single channel current by 15%. Both barbiturates decrease the duration of openings within a burst but have only a small effect on the burst duration. Macroscopic currents were activated by rapid perfusion of 300 microM acetylcholine to outside-out patches. The concentration dependence of peak current inhibition was fit with a Hill function; for pentobarbital, Ki = 32 microM, n = 1.09; for barbital, Ki = 1900 microM, n = 1.24. Inhibition is voltage independent. The kinetics of inhibition by pentobarbital are at least 30 times faster than inhibition by barbital (3 ms vs. < 0.1 ms at the Ki). Pentobarbital binds > or = 10-fold more tightly to open channels than to closed channels; we could not determine whether the binding of barbital is state dependent. Experiments performed with both barbiturates reveal that they do not compete for a single binding site on the acetylcholine receptor channel protein, but the binding of one barbiturate destabilizes the binding of the other. These results support a kinetic model in which barbiturates bind to both open and closed states of the AChR and block the flow of ions through the channel. An additional, lower-affinity binding site for pentobarbital may explain the effects seen at > 100 microM pentobarbital.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9089445&dopt=Abstract barbiturate Butalbital Fioricet





Analeptic use in clinical toxicology: a historical appraisal.

Wax PM.

Department of Emergency Medicine, University of Rochester School of Medicine, NY 14642, USA.

BACKGROUND: The introduction and increasing popularity of the barbiturates during the first two decades of the 20th century was associated with a new life threatening toxicological problem: the barbiturate overdose. METHODS: This paper reviews the four major phases of analeptic use. As interest in the principles of physiologic antagonism between stimulants and depressants grew, analeptic agents were increasingly used to treat the obtundation and respiratory depression of barbiturate overdose. At first, naturally occurring stimulants such as camphor, strychnine, picrotoxin, and caffeine were used in desperate attempts to awaken patients. During the 1930s, and continuing at some centers into the 1960s, an increasing number of synthetic analeptics agents such as nikethamide, pentylenetetrazol, bemegride, amphetamine, and methylphenidate were enthusiastically recommended as barbiturate antidotes, often at very high doses. Unfortunately, utilizing generous amounts of multiple convulsants was not without its share of complications. Using this analeptic strategy the mortality rate after moderate to severe barbiturate overdose remained as high as 45%. Beginning in the mid-1940s a group of Scandinavian physicians pioneered a revolutionary approach to sedativehypnotic overdose that rejected the use of analeptics and relied on respiratory ventilation and supportive care. CONCLUSIONS: Although barbiturate overdose mortality decreased to less than 1% using this strategy, it would take another 20 years before this technique was universally adapted. While analeptic therapies for the treatment of drug overdose have now been abandoned, one of these analeptics, methylphenidate, currently enjoys wide use in the treatment of attention deficit hyperactivity disorder.

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Barbiturate anticonvulsants: a neuropsychological and quantitative electroencephalographic study.

Willis J, Nelson A, Black FW, Borges A, An A, Rice J.

Department of Psychiatry and Neurology, Tulane University Medical School, New Orleans, LA 70112, USA.

We studied 11 epileptic children aged 7 to 14 years with quantitative electroencephalographic (EEG) and neuropsychological tests, both on and off the barbiturate anticonvulsants phenobarbital and mephobarbital, comparing them to 13 controls matched for age and IQ who received testing at similar intervals. Neuropsychological tests employed were the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt, controlled oral word association test (COWAT), selected subtests of the Wechsler Memory Scale-Revised, Purdue Peg Board, Stroop Test, Trail Making Test, Wide Range Achievement Test-Revised, and Achenbach Behavior Rating Scale. There was no difference between on- and off-drug quantitative EEG in percentage power of any frequency band between 0.6 and 32 Hz. Neuropsychological data from all 11 subjects were analyzed with a two-factor analysis of variance with repeated measures on the time factor. The only difference from controls was on the Stroop Test. Parents reported clear behavioral changes in 6 of 11 subjects, but in 4 of these children the behavioral changes were sufficiently mild that parents chose to continue the barbiturate anticonvulsants: irritability, oppositional attitude, and overactivity were described. Mephobarbital was reported by parents to cause less severe problems than phenobarbital in subjects who had taken both barbiturate anticonvulsants. Barbiturate anticonvulsants have no effect on quantitative EEG and limited effects on neuropsychological tests in school-aged children.

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