%0 Journal Article %1 Lohse1987 %A Lohse, M. J. %A Boser, S. %A Klotz, K. N. %A Schwabe, U. %D 1987 %J Naunyn Schmiedebergs Arch Pharmacol %K *Bicyclo Animals Barbiturates/*metabolism/pharmacology Bicyclo Binding, Brain/metabolism Competitive Compounds, Compounds/metabolism Diazepam/metabolism GABA-A/*metabolism/physiology Heterocyclic Male Methohexital/pharmacology Phenylisopropyladenosine/metabolism Purinergic/*metabolism/physiology Rats Strains Receptor Mice %N 2 %P 211-7 %T Affinities of barbiturates for the GABA-receptor complex and A1 adenosine receptors: a possible explanation of their excitatory effects %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2825044 %V 336 %X The effects of barbiturates on the GABA-receptor complex and the A1 adenosine receptor were studied. At the GABA-receptor complex the barbiturates inhibited the binding of 35St-butylbicyclophosphorothionate (35STBPT) and enhanced the binding of 3Hdiazepam. Kinetic and saturation experiments showed that both effects were allosteric. Whereas all barbiturates caused complete inhibition of 35STBPT binding, they showed varying degrees of maximal enhancement of 3Hdiazepam binding; (+/-)methohexital was identified as the most efficacious compound for this enhancement. At the A1 adenosine receptor all barbiturates inhibited the binding of 3HN6-phenylisopropyladenosine (3HPIA) in a competitive manner. The comparison of the effects on 3Hdiazepam and 3HPIA binding showed that excitatory barbiturates interact preferentially with the A1 adenosine receptor, and sedative/anaesthetic barbiturates with the GABA-receptor complex. It is speculated that the interaction with these two receptors might be the basis of the excitatory versus sedative/anaesthetic properties of barbiturates.

@article{Lohse1987, abstract = {The effects of barbiturates on the GABA-receptor complex and the A1 adenosine receptor were studied. At the GABA-receptor complex the barbiturates inhibited the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPT) and enhanced the binding of [3H]diazepam. Kinetic and saturation experiments showed that both effects were allosteric. Whereas all barbiturates caused complete inhibition of [35S]TBPT binding, they showed varying degrees of maximal enhancement of [3H]diazepam binding; (+/-)methohexital was identified as the most efficacious compound for this enhancement. At the A1 adenosine receptor all barbiturates inhibited the binding of [3H]N6-phenylisopropyladenosine ([3H]PIA) in a competitive manner. The comparison of the effects on [3H]diazepam and [3H]PIA binding showed that excitatory barbiturates interact preferentially with the A1 adenosine receptor, and sedative/anaesthetic barbiturates with the GABA-receptor complex. It is speculated that the interaction with these two receptors might be the basis of the excitatory versus sedative/anaesthetic properties of barbiturates.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lohse, M. J. and Boser, S. and Klotz, K. N. and Schwabe, U.}, biburl = {https://www.bibsonomy.org/bibtex/23bed3e5903d2e8632038cd3cb224fd62/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {484a0104721d2d82e3f0d3fb701d3f97}, intrahash = {3bed3e5903d2e8632038cd3cb224fd62}, issn = {0028-1298 (Print) 0028-1298 (Linking)}, journal = {Naunyn Schmiedebergs Arch Pharmacol}, keywords = {*Bicyclo Animals Barbiturates/*metabolism/pharmacology Bicyclo Binding, Brain/metabolism Competitive Compounds, Compounds/metabolism Diazepam/metabolism GABA-A/*metabolism/physiology Heterocyclic Male Methohexital/pharmacology Phenylisopropyladenosine/metabolism Purinergic/*metabolism/physiology Rats Strains Receptor Mice}, month = Aug, note = {Lohse, M J Boser, S Klotz, K N Schwabe, U In Vitro Research Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1987 Aug;336(2):211-7.}, number = 2, pages = {211-7}, shorttitle = {Affinities of barbiturates for the GABA-receptor complex and A1 adenosine receptors: a possible explanation of their excitatory effects}, timestamp = {2010-12-14T18:22:56.000+0100}, title = {Affinities of barbiturates for the GABA-receptor complex and A1 adenosine receptors: a possible explanation of their excitatory effects}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2825044}, volume = 336, year = 1987 }