Drugs online research references
Brain Res. 1982 Dec 9;252(2):227-37.
Septal modulation of the population spike in the fascia dentata produced by perforant path stimulation in the rat.
Fantie BD, Goddard GV.
Electrical stimulation of the perforant path, which originates in the entorhinal cortex, produces a characteristic excitatory postsynaptic field potential (extracellular EPSP) which can be recorded in the fascia dentata. This evoked response may include a population spike, if stimulation is sufficient. In the anaesthetized rat, stimulation of the medial septum, when paired with perforant path stimulation, was found to augment the population spike component of the evoked field potential. Stimulation of the septum alone produced no apparent field potential. The augmentation effect was found to have a rapid onset (4 ms), which is sufficient for the participation of interneurons, and a relatively long time course (150 ms). Presynaptic mechanisms of facilitation were ruled out as there was no concurrent alteration of the extracellular EPSP. A change in population spike threshold, compatible with a postsynaptic mechanism, was observed and some possible models of action discussed. Augmentation survived depletion of hippocampal norepinephrine caused by injections of 6-hydroxydopamine into the dorsal noradrenergic bundle, indicating that the facilitation was not due to an activation of the ascending noradrenergic fibres of passage originating from the locus coeruleus. The cholinergic septo-hippocampal pathway was ruled out as a likely candidate for the modulation as the augmentation survived injections of the muscarinic antagonists atropine and scopolamine and the nicotinic antagonists tubocurarine and dihydro-beta-erythroidine. A relationship between the septal modulation and hippocampal theta was suggested.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6817846&dopt=Abstract
Eur J Pharmacol. 1993 Sep 7;241(1):27-34.
Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196, a putative cognitive enhancer.
Matsuoka N, Yamaguchi I, Satoh M.
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
N-(4-Acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide (FR121196), a newly introduced putative cognitive enhancer of a derivative of piperazine, was investigated for its effects on long-term potentiation in guinea-pig hippocampal slices. The magnitude of long-term potentiation of population spikes recorded in CA3 pyramidal neurons was significantly augmented by perfusing FR121196 (10(-9)-10(-6) M) for 25 min before and during tetanic stimulation of the mossy fibers; the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose-response curve was bell-shaped with a maximal augmentation at 10(-7) M. Similar activity and bell-shaped dose-response curve were observed with methamphetamine (10(-8)-10(-6) M). Physostigmine (10(-8)-10(-6) M) also facilitated long-term potentiation of this pathway and the magnitude of augmentation was concentration-dependent. Scopolamine (10(-6) M) per se had little effect on the magnitude of long-term potentiation in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FR121196 (10(-7) M) and physostigmine (10(-6) M), although it failed to influence that by methamphetamine (10(-7) M). In hippocampal slices from animals treated with cysteamine, which was shown to deplete hippocampal somatostatin, FR121196 (10(-7) M) hardly affected long-term potentiation generation, whereas physostigmine (10(-6) M) and methamphetamine (10(-7) M) augmented it significantly. These results suggest that FR121196 enhances the development of long-term potentiation in the mossy fiber-CA3 pathway through activation of somatostatinergic neurons in the hippocampal formation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7901036&dopt=Abstract
Eur J Pharmacol. 1989 Nov 28;173(1):35-42.
Presynaptic and postjunctional muscarinic receptors in dog ileum: binding studies.
Kostka P, Kwan CY, Daniel EE.
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
[3H]N-Methylscopolamine identified two distinct populations of muscarinic receptors in membranes derived from the longitudinal smooth muscle/myenteric plexus of dog ileum. In isolated axonal varicosities, the half-maximal saturation of binding sites occurred at 2.38 +/- 0.39 nM [3H]N-methylscopolamine, with maximal binding capacity 140 +/- 35 fmol/mg protein (mean +/- S.D., n = 8). In purified smooth muscle plasma membranes, the Kd value was 16 +/- 3 nM with Bmax 1960 +/- 494 fmol/mg. The displacement potencies of subtype-selective muscarinic antagonists in the fraction of axonal varicosities followed the order 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methiodide much greater than pirenzepine = methoctramine greater than AF-DX 116 with pKi values 7.38, 5.67, 5.70 and 5.13, respectively. Both 4-DAMP methiodide and pirenzepine were approximately 4-fold less potent in displacing the ligand from the receptors in smooth muscle plasma membranes as compared to varicose receptors. The potency ratios of cardioselective antagonists methoctramine and AF-DX 116 on varicose and smooth muscle receptors were 1 and 1.7. It is concluded that presynaptic receptors located on isolated axonal varicosities have pharmacological properties similar to glandular (M3) subtype of muscarinic receptors. The binding properties of receptors present in smooth muscle plasma membranes were found incompatible with those of any of the M1, M2 or M3 subtypes.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2606155&dopt=Abstract
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