Inhibition of GABA and benzodiazepine receptor binding by penicillins

Penicillins are thought to be GABA receptor antagonists. In order to determine the affinities of various penicillin derivatives for the GABA receptor, their potencies as inhibitors of specific [3H]GABA binding to rat brain membranes were investigated. All investigated penicillins inhibit specific [3H]GABA binding, with IC50 values ranging from 2 to 60 mM. The results are consistent with the assumption that penicillins are weak GABA receptor antagonists.

[1]  D. Wong,et al.  γ‐AMINOBUTYRTC ACID RECEPTORS IN CEREBELLAR MEMBRANES OF RAT BRAIN AFTER A TREATMENT WITH TRITON X‐100 1 , 1979 .

[2]  A. Guidotti,et al.  Molecular mechanisms in the receptor action of benzodiazepines. , 1979, Annual review of pharmacology and toxicology.

[3]  Solomon H. Snyder,et al.  Influences of Ions, Enzymes, and Detergents on γ-Aminobutyric Acid-Receptor Binding in Synaptic Membranes of Rat Brain , 1977 .

[4]  R. A. Davidoff.  Penicillin and inhibition in the cat spinal cord. , 1972, Brain research.

[5]  R. Olsen,et al.  Effects of drugs on γ-aminobutyric acid receptors, uptake, release and synthesis in vitro , 1978, Brain Research.

[6]  U. Wollert,et al.  [3H] Flunitrazepam: its advantages as a ligand for the identification of benzodiazepine receptors in rat brain membranes. , 1978, Research communications in chemical pathology and pharmacology.

[7]  S. Snyder,et al.  Muscarinic cholinergic binding in rat brain. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. R. Curtis,et al.  Convulsive action of penicillin. , 1972, Brain research.

[9]  B. Hochner,et al.  Penicillin decreases chloride conductance in crustacean muscle: a model for the epileptic neuron , 1976, Brain Research.

[10]  J. Barker,et al.  Specific antagonism of GABA‐mediated postsynaptic inhibition in cultured mammalian spinal cord neurons , 1978, Neurology.

[11]  W. A. Wilson,et al.  Common synaptic effects of pentylenetetrazol and penicillin. , 1974, Brain research.

[12]  J. Barker,et al.  Pentylenetetrazol and penicillin are selective antagonists of GABA-mediated post-synaptic inhibition in cultured mammalian neurones , 1977, Nature.

[13]  M. Gutnick,et al.  Relative convulsant potencies of structural analogues of penicillin , 1976, Brain Research.