Showing papers on "Barbiturate published in 2004"

Selective GABA-receptor actions of amobarbital on thalamic neurons.

Abstract: We studied amobarbital's effects on membrane properties and currents, and electrically evoked inhibitory postsynaptic currents (IPSCs) mediated by γ-aminobutyric acid (GABA) in rat thalamic slices. Using concentration–response relationships, we compared amobarbital's effects in nociceptive nuclei and non-nociceptive nucleus reticularis thalami (nRT). Amobarbital decreased input resistance by activating GABAA receptors. Amobarbital produced a larger decrease in ventrobasal than nRT neurons. Amobarbital depressed burst and tonic firing. Depression of burst firing was more effective, particularly in ventrobasal and intralaminar neurons. Depression was reversed by GABAA antagonists, and surmountable by increasing current injection, implicating a receptor-mediated shunt mechanism. Amobarbital did not affect the tetrodotoxin-isolated low threshold Ca2+ spike during GABAA blockade. Amobarbital reduced excitability without altering outward leak, or hyperpolarisation-activated inward currents. Amobarbital increased mean conductance and burst duration of single GABAA channels. Consistent with this, amobarbital increased amplitude and decay time of IPSCs with distinct EC50s, implicating actions at two GABAA receptor sites. Activation of GABAA receptors by low concentrations, fast IPSC amplitude modulation, and failure to affect intrinsic currents distinguished amobarbital's mechanism of action from previously characterised barbiturates. The selective actions of amobarbital on GABAA receptor may have relevance in explaining anaesthetic and analgesic uses. British Journal of Pharmacology (2004) 143, 485–494. doi:10.1038/sj.bjp.0705974

Un siglo de barbit´uricos en neurología

Abstract: Introduction and aims. Until the early 20th century, pharmacological treatments for neurological disorders were scarce and inefficient; only bromides stood out as sedating and antiepileptic agents. Development The introduction of barbiturates for clinical use in 1904 heralded the beginning of a new age in the pharmacological management of certain neurological pathologies. In this study, we analyse the historical process of the discovery and use of barbiturates in the field of neurology, from the moment it was started by von Baeyer in 1864, with the synthesis of malonylurea, up to the period of the decline of barbiturate therapy in the 1960s. In 1903, von Mering and Fischer discovered the hypnotic properties of barbital and later synthesised phenobarbital (1911). In the years that followed a number of barbiturates, such as butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, and so on, were gradually incorporated into the therapeutic arsenal. During this period, the different therapeutic uses of barbiturates in neurology were analysed, from their traditional use as hypnotic agents (von Husen) to the discovery of the anticonvulsant properties of phenobarbital (Hauptmann) and its use in the treatment of epilepsy. Conclusions. The barbiturates were one of the first pharmacological tools that proved to be really effective in the management of some neurological disorders. Nevertheless, problems associated with their safety (dependence phenomena and deaths from overdoses), together with the introduction of numerous psychopharmacological agents in the 1950s, ended up eclipsing the use of barbiturates, except for a few very specific cases in which they are still indicated.