High-Affinity, Selective σ Ligands of the 1,2,3,4-Tetrahydro-1,4′-silaspiro[naphthalene-1,4′-piperidine] Type: Syntheses, Structures, and Pharmacological Properties

ChemMedChem ◽  
2011 ◽  
Vol 7 (3) ◽  
pp. 523-532 ◽  
Author(s):  
Reinhold Tacke ◽  
Rüdiger Bertermann ◽  
Christian Burschka ◽  
Steffen Dörrich ◽  
Markus Fischer ◽  
...  
Keyword(s):  
Pharmacological Properties ◽  
High Affinity

scholarly journals Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2126
Author(s):  
Battistina Asproni ◽  
Gabriele Murineddu ◽  
Paola Corona ◽  
Gérard A. Pinna
Keyword(s):  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Receptor Interaction ◽  
Pharmacological Properties ◽  
Cb2 Receptor ◽  
Antiemetic Effect ◽  
High Affinity ◽  
Cb1 Antagonist ◽  
Cb2 Receptors ◽  
Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

scholarly journals GluN2 Subunit-Dependent Redox Modulation of NMDA Receptor Activation by Homocysteine

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1441
Author(s):  
Dmitry A. Sibarov ◽  
Sergei I. Boikov ◽  
Tatiana V. Karelina ◽  
Sergei M. Antonov
Keyword(s):  
Disulfide Bonds ◽  
Receptor Activation ◽  
Pharmacological Properties ◽  
Patch Clamp Recording ◽  
Redox Modulation ◽  
High Affinity ◽  
Wide Range ◽  
Nmdar Activation ◽  
Nmda Receptor Activation ◽  
Glun2 Subunit

Homocysteine (HCY) molecule combines distinct pharmacological properties as an agonist of N-methyl-d-aspartate receptors (NMDARs) and a reducing agent. Whereas NMDAR activation by HCY was elucidated, whether the redox modulation contributes to its action is unclear. Here, using patch-clamp recording and imaging of intracellular Ca2+, we study dithiothreitol (DTT) effects on currents and Ca2+ responses activated by HCY through native NMDARs and recombinant diheteromeric GluN1/2A, GluN1/2B, and GluN1/2C receptors. Within a wide range (1–800 μM) of [HCY]s, the concentration–activation relationships for recombinant NMDARs revealed a biphasicness. The high-affinity component obtained between 1 and 100 µM [HCY]s corresponding to the NMDAR activation was not affected by 1 mM DTT. The low-affinity phase observed at [HCY]s above 200 μM probably originated from thiol-dependent redox modulation of NMDARs. The reduction of NMDAR disulfide bonds by either 1 mM DTT or 1 mM HCY decreased GluN1/2A currents activated by HCY. In contrast, HCY-elicited GluN1/2B currents were enhanced due to the remarkable weakening of GluN1/2B desensitization. In fact, cleaving NMDAR disulfide bonds in neurons reversed the HCY-induced Ca2+ accumulation, making it dependent on GluN2B- rather than GluN2A-containing NMDARs. Thus, estimated concentrations for the HCY redox effects exceed those in the plasma during intermediate hyperhomocysteinemia but may occur during severe hyperhomocysteinemia.

A-85380 [3-(2(S)-azetidinylmethoxy) pyridine]: In Vitro pharmacological properties of a novel, high affinity α4β2 nicotinic acetylcholine receptor ligand

1996 ◽  
Vol 35 (6) ◽  
pp. 725-734 ◽  
Author(s):  
James P. Sullivan ◽  
Diana Donnelly-Roberts ◽  
Clark A. Briggs ◽  
David J. Anderson ◽  
Murali Gopalakrishnan ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Pharmacological Properties ◽  
Receptor Ligand ◽  
Nicotinic Acetylcholine ◽  
High Affinity

Vasoactive intestinal peptide and its receptors in fetuses with cystic fibrosis

1989 ◽  
Vol 257 (4) ◽  
pp. G561-G569 ◽  
Author(s):  
E. Chastre ◽  
W. Bawab ◽  
C. Faure ◽  
S. Emami ◽  
F. Muller ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Vasoactive Intestinal Peptide ◽  
G Proteins ◽  
Binding Sites ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Adenylate Cyclase System ◽  
High Affinity ◽  
Signal Transduction Cascade ◽  
Molecular Components

Fetuses were investigated to establish whether vasoactive intestinal peptide (VIP) and its receptors are involved in the basic biochemical defect causing cystic fibrosis (CF). The intestine was used as a target for the disease and the liver as control. The immunoreactive and biologically active VIP contents of the colon and lower part of the small intestine were 1.5-2.5 times higher in CF fetuses than in controls. In control and CF intestinal mucosa, there was no change in the Scatchard parameters of the 125I-labeled VIP binding sites (Kd = 4.7-6.1 X 10(-11) M; Bmax = 268-280 fmol/mg protein for the high-affinity sites), in the two molecular components constituting the cross-linked 125I-VIP binding (Mr = 66,000 and 30,000), or in the pharmacological properties and functional characteristics of the VIP receptors activating the G proteins-adenylate cyclase system (Ka = 0.7 X 10(-9) M VIP). Similar results were obtained in liver. These findings suggest that neither VIP nor its receptors are involved in CF intestine. The possible involvement of other effectors related to the VIP pathway in CF intestine, including the release of VIP and adenosine 3',5'-cyclic monophosphate signal-transduction cascade, are presented.

Sila-Analogues of High-Affinity, Selective σ Ligands of the Spiro[indane-1,4‘-piperidine] Type:  Syntheses, Structures, and Pharmacological Properties

2003 ◽  
Vol 22 (5) ◽  
pp. 916-924 ◽  
Author(s):  
Reinhold Tacke ◽  
Vera I. Handmann ◽  
Rüdiger Bertermann ◽  
Christian Burschka ◽  
Martin Penka ◽  
...  
Keyword(s):  
Pharmacological Properties ◽  
High Affinity

Contraceptive and therapeutic effects of combined oral contraceptive with drospirenone

2020 ◽  
pp. 6-9
Author(s):  
T. V. Ovsyannikova ◽  
I. A. Kulikov
Keyword(s):  
Premenstrual Syndrome ◽  
Unwanted Pregnancy ◽  
Progesterone Receptors ◽  
Therapeutic Effects ◽  
Pharmacological Properties ◽  
Polycystic Ovaries ◽  
Combined Oral Contraceptives ◽  
High Affinity ◽  
Combined Oral Contraceptive ◽  
Contraceptive Effect

The article presents data on the clinical and contraceptive capabilities of an estrogen-progestogen drug containing drospirenone (Midiana). By its pharmacological properties, drospirenone is close to endogenous progesterone and has gestagenic, antiandrogenic and antimineralocorticoid action. With a high affinity for progesterone receptors, drospirenone suppresses ovulation, reliably protects against unwanted pregnancy and provides an additional contraceptive effect. Combined oral contraceptives with drospirenone, taking into account their antiandrogenic and antimineralocorticoid properties, are successfully used in the treatment of premenstrual syndrome, polycystic ovaries, hyperandrogenism and in the prevention of endometrial hyperplastic processes without causing significant weight change.

Synthesis and Pharmacological Properties of Novel 8-Substituted Imidazobenzodiazepines:  High-Affinity, Selective Probes for α5-Containing GABAAReceptors1

1996 ◽  
Vol 39 (9) ◽  
pp. 1928-1934 ◽  
Author(s):  
Ruiyan Liu ◽  
Rona J. Hu ◽  
Puwen Zhang ◽  
Phil Skolnick ◽  
James M. Cook
Keyword(s):  
Pharmacological Properties ◽  
High Affinity

Synthesis and Pharmacological Properties of 11-Hydroxy-3-(1',1'-dimethylheptyl)hexahydrocannabinol: A High Affinity Cannabinoid Agonist

1994 ◽  
Vol 37 (16) ◽  
pp. 2619-2622 ◽  
Author(s):  
Guo Yan ◽  
Dali Yin ◽  
Atmaram D. Khanolkar ◽  
David R. Compton ◽  
Billy R. Martin ◽  
...  
Keyword(s):  
Pharmacological Properties ◽  
High Affinity ◽  
Cannabinoid Agonist

Neuronal and Extraneuronal Uptake of 3H-Norepinephrine in the Heart of the Active Bat: An Electron Microscopic Radioautographic Study

1973 ◽  
Vol 31 ◽  
pp. 522-523
Author(s):  
Martin Hagopian ◽  
Michael D. Gershon ◽  
Eladio A. Nunez
Keyword(s):  
Smooth Muscle ◽  
Monoamine Oxidase ◽  
Vascular Smooth Muscle ◽  
Cardiac Muscle ◽  
Maximum Rate ◽  
External Medium ◽  
Extraneuronal Uptake ◽  
Electron Microscopic ◽  
Cardiac Tissues ◽  
High Affinity

The ability of cardiac tissues to take up norepinephrine from an external medium is well known. Two mechanisms, called Uptake and Uptake respectively by Iversen have been differentiated. Uptake is a high affinity system associated with adrenergic neuronal elements. Uptake is a low affinity system, with a higher maximum rate than that of Uptake. Uptake has been associated with extraneuronal tissues such as cardiac muscle, fibroblasts or vascular smooth muscle. At low perfusion concentrations of norepinephrine most of the amine taken up by Uptake is metabolized. In order to study the localization of sites of norepinephrine storage following its uptake in the active bat heart, tritiated norepinephrine (2.5 mCi; 0.064 mg) was given intravenously to 2 bats. Monoamine oxidase had been inhibited with pheniprazine (10 mg/kg) one hour previously to decrease metabolism of norepinephrine.

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