Effect of nootropic dipeptide noopept on CA1 pyramidal neurons involves α7AChRs on interneurons in hippocampal slices from rat.

Noopept (NP) is a proline-containing dipeptide with nootropic and neuroprotective properties. We have previously shown that NP significantly increased the frequency of spontaneous IPSCs in hippocampal CA1 pyramidal cells mediated by the activation of inhibitory interneurons in stratum radiatum. The cholinergic system plays an important role in the performance of cognitive functions, furthermore multiple behavioral and clinical facts link NP with the cholinergic system.

Synthesis and evaluation of avermectin-imidazo[1,2-a]pyridine hybrids as potent GABA receptor modulators.

The γ-aminobutyric acid type A (GABA) receptors are pentameric transmembrane protein complexes. They have attracted extensive attention from the scientific community due to their significant pharmacological potential. Here we report the first synthesis of avermectin-imidazo[1,2-a]pyridine hybrids promising as GABA receptor positive allosteric modulators (PAMs).

Development of 1,3-thiazole analogues of imidazopyridines as potent positive allosteric modulators of GABA receptors.

Structure-activity relationship studies were conducted in the search for 1,3-thiazole isosteric analogs of imidazopyridine drugs (Zolpidem, Alpidem). Three series of novel γ-aminobutyric acid receptor (GABAR) ligands belonging to imidazo[2,1-b]thiazoles, imidazo[2,1-b][1,3,4]thiadiazoles, and benzo[d]imidazo[2,1-b]thiazoles were synthesized and characterized as active agents against GABAR benzodiazepine-binding site. In each of these series, potent compounds were discovered using a radioligand competition binding assay.

The mechanisms of potentiation and inhibition of GABA receptors by non-steroidal anti-inflammatory drugs, mefenamic and niflumic acids.

Fenamates mefanamic and niflumic acids (MFA and NFA) induced dual potentiating and inhibitory effects on GABA currents recorded in isolated cerebellar Purkinje cells using the whole-cell patch-clamp and fast-application techniques. Regardless of the concentration, both drugs induced a pronounced prolongation of the current response. We demonstrated that the same concentration of drugs can produce both potentiating and inhibitory effects, depending on the GABA concentration, which indicates that both processes take place simultaneously and the net effect depends on the concentrations of both the agonist and fenamate.

Block of GABA(A) receptor ion channel by penicillin: electrophysiological and modeling insights toward the mechanism.

GABA(A) receptors (GABA(A)R) mainly mediate fast inhibitory neurotransmission in the central nervous system. Different classes of modulators target GABA(A)R properties. Penicillin G (PNG) belongs to the class of noncompetitive antagonists blocking the open GABA(A)R and is a prototype of β-lactam antibiotics.

Modulation of ATP-induced currents by zinc in acutely isolated hypothalamic neurons of the rat.

1. Whole-cell patch-clamp and fast perfusion were used to study the effects of zinc on adenosine 5'-triphosphate (ATP)-induced responses of histaminergic neurons. 2.

Expression and function of P2X purinoceptors in rat histaminergic neurons.

(1) The pharmacology of ATP responses and the expression pattern of seven known subunits of the P2X receptor were investigated in individual histaminergic neurons of the tuberomamillary nucleus (TM). (2) ATP (3-1000 micro M) evoked fast non-desensitizing inward currents in TM neurons. 2-methylthioATP (2MeSATP) displayed the same efficacy but a lower potency, EC(50)s 84 micro M versus 48 micro M, when compared with ATP.

GABA(A) receptor heterogeneity in histaminergic neurons.

Histaminergic neurons of the tuberomamillary nucleus display pacemaker properties; their firing rate is regulated according to behavioural state by gabaergic inhibition. Whole-cell recordings and single-cell RT-PCR from acutely isolated rat tuberomamillary neurons were used to characterize GABA -evoked currents and to correlate them with the expression pattern of 12 GABAA receptor subunits. We report differences in sensitivity to GABA and zinc as well as in the modulation of IPSC-decay times by zolpidem in histaminergic neurons expressing gamma-subunits at different levels.

Mechanisms of GABA(A) receptor blockade by millimolar concentrations of furosemide in isolated rat Purkinje cells.

The action of diuretic furosemide on the GABA(A) receptor was studied in acutely isolated Purkinje cells using the whole-cell recording and fast application system. Furosemide blocked stationary component of GABA-activated currents in a concentration-dependent manner with IC(50) value > 5 mM at -70 mV. The inhibition was rapid in the onset, fully reversible and did not require drug pre-perfusion.