Voltage-clamp evidence of GABA receptor subunit-specific effects: pharmacodynamic fingerprint of chlornordiazepam, the major active metabolite of mexazolam, as compared to alprazolam, bromazepam, and zolpidem.

Background: Anxiolytic benzodiazepines, due to their clinical effectiveness, are one of the most prescribed drugs worldwide, despite being associated with sedative effects and impaired psychomotor and cognitive performance. Not every GABA receptor functions in the same manner. Those containing α1 subunits are associated with sleep regulation and have a greater effect on the sedative-hypnotic benzodiazepines, whereas those containing α2 and/or α3 subunits are associated with anxiety phenomena and have a greater effect on the anxiolytic benzodiazepines.

Sustained postsynaptic kainate receptor activation downregulates AMPA receptor surface expression and induces hippocampal LTD.

It is well established that long-term depression (LTD) can be initiated by either NMDA or mGluR activation. Here we report that sustained activation of GluK2 subunit-containing kainate receptors (KARs) leads to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) endocytosis and induces LTD of AMPARs (KAR-LTD) in hippocampal neurons. The KAR-evoked loss of surface AMPARs is blocked by the ionotropic KAR inhibitor UBP 310 indicating that KAR-LTD requires KAR channel activity.

Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus.

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus.

Methadone: does it really have low efficacy at micro-opioid receptors?

There is confusion in the literature concerning the relative agonist efficacy of methadone at micro-opioid receptors (MOPrs). Here, we confirm that methadone is a full agonist in guanosine 5'-O-[gamma-thio]triphosphate (GTPgammaS) binding studies. Methadone, however, seems to have low efficacy in studies of MOPr activation of G-protein-gated potassium (GIRK) channels, but this is because it directly inhibits the GIRK channels.

C-terminal splice variants of the mu-opioid receptor: existence, distribution and functional characteristics.

The distribution of the mRNA of different C-terminal splice variants of the mu-opioid receptor in rat CNS was assessed by RT-PCR. The mRNA species for MOR1, MOR1A and MOR1B were readily detectable and distributed widely throughout the rat CNS, with levels of MOR1 and MOR1A mRNA being overall greater than for MOR1B. We did not find convincing evidence that significant levels of MOR1C, MOR1C1, MOR1C2 and MOR1D are present in rat CNS.