Studies on the relationship of binding affinity to psychoactive and anticholinergic potency of a group of psychotomimetic glycolates

Baumgold, Jesse; Abood, Leo G.; Aronstam, Robert S.

doi:10.1016/0006-8993(77)90889-7

Cited by 26 publications

(5 citation statements)

References 15 publications

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“…Table 1 shows that the binding of 1 ~M -[~H ] Q N B was inhibited far more strongly by the biologically active (-) isomer of QNB. This has been shown previously for the rat brain muscarinic receptor (Baumgold et al, 1977). It distinguishes the house fly head QNB binding site from the QNB binding site on human erythrocytes on which the two isomers were equally active.…”

Section: Resultssupporting

confidence: 67%

Quinuclidinyl Benzilate Binding in House Fly Heads and Rat Brain

Jones

Sumikawa

1981

Journal of Neurochemistry

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House fly heads contain a binding site for 3-quinuclidinyl benzilate (QNB) that is quite similar in pharmacology to the muscarinic acetylcholine receptor of vertebrate tissues. The house fly site binds [3H]QNB reversibly with a Kd of 260 pM and Bmax of 1 pmol/g of heads from direct binding measurements. The Kd calculated from the ratio of the dissociation rate constant (2 x 10(-4)sec-1) to the association rate constant (2.5 x 10(6) M-1sec-1) was 80 pM. The house fly site binds (-)quinuclidinyl benzilate preferentially, as do classic muscarinic receptors. The binding is also sensitive to other muscarinic antagonists and agonists. Nicotinic and other drugs are no more effective on the house fly site than they are on the rat brain muscarinic receptor itself. These binding studies suggest that the house fly QNB binding site is a muscarinic receptor.

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Section: Resultssupporting

confidence: 67%

Quinuclidinyl Benzilate Binding in House Fly Heads and Rat Brain

Jones

Sumikawa

1981

Journal of Neurochemistry

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“…Figure 4 showing the plot of -log Kj (con centrations of agonists and antagonists which displace bound ( 'H)-QNB by 50%) versus the reciprocal of ED50 or IDS0 (concentrations of agonists and antagonists which stimulate or in hibit amylase release) is an attempt to establish a correlation between the two parameters. Baumgold et al (2) has used this method to establish a relationship between binding to psychoactive receptors and anticholinergic potency of a group of psychotomimetic glycolates in rat brain. The fact that we found a very good correlation both for agonist and antag onist between the binding and the secretory studies suggests that the binding sites and those involved in the cholinergic control of pancreatic enzyme secretion are similar.…”

Section: Discussionmentioning

confidence: 99%

Muscarinic Receptors of the Pancreas: a Correlation between Displacement of (<sup>3</sup>H)-Quinuclidinyl Benzilate Binding and Amylase Secretion

Morisset

Poirier

1979

Pharmacology

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(³H)-quinuclidinyl benzilate [(³H)-QNB], a potent muscarinic antagonist, was used as a tool to reveal the presence of muscarinic receptors in rat pancreas. Binding assays were performed on a 49,000 g pellet. Known muscarinic antagonists and agonists were used for competition assays on (³H)-QNB binding and studies on amylase secretion in vitro. A correlation was established between the binding assays and the studies on amylase release which suggests that the binding sites and those involved in the cholinergic control of pancreatic enzyme secretion are similar.

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“…Muscarinic receptors are particularly compelling as therapeutic targets for the treatment of schizophrenia based on evidence that muscarinic antagonists produce a psychosis in humans with symptoms similar to the positive and negative behaviors and cognitive deficits associated with the disease. − Hallucinations are one of the most debilitating components of schizophrenia and degenerative neurological diseases. Certain drugs and substances of abuse can induce hallucinations in humans suggesting that receptors for these compounds may play a role in generating hallucinations and may be attractive therapeutic targets to treat these debilitating symptoms.…”

Section: Schizophreniamentioning

confidence: 99%

Therapeutic Opportunities for Muscarinic Receptors in the Central Nervous System

et al. 2000

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Background: Diabetic retinopathy (DR) has become a worldwide concern in recent years because of the high prevalence and vision-threat. The limited therapies have been in stark contrast to its high prevalence. On top of that, almost all the treatments, like laser, are applied only at the end stage of this disease. However, with the development of network pharmacology, a traditional Chinese medicine (TCM), Compound Danshen Dripping Pill (CDDP), may bring some new insights into the early intervention of DR. Methods: The active compounds and potential targets of CDDP and DR-related targets were collected from the TCMSP, UniProt, GeneCards and OMIM databases. And protein-protein interactions (PPI) information was achieved from the STRING database. The gene enrichment analysis of GO and KEGG was carried out by "clusterPro ler" in R software. The collected data was then used to form network maps of compound-target and PPI, or visualized by the software of Cytoscape. Results: 54 compounds and 50 targets were identi ed for CDDP against DR. Among the predicted effective compounds, 29 tanshinones from Radix Salviae (Danshen) were identi ed. And the core targets might be estrogen receptor (ESR1), androgen receptor (AR), caspase-3 (CASP3), Interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) in 50 targets. There were 266 signi cantly correlated biological processes such as steroid hormone response, oxidative stress and apoptosis enriched out. Besides, The 50 targets signi cantly participate in 97 pathways and mainly enriched in advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE), uid shear stress and atherosclerosis, apoptosis and VEGF signal pathway et al. Conclusions: The mechanisms of CDDP for treating DR may involve multi-compound, multi-target and multi-pathway synergistic effects. It may participate in the regulation of steroid hormone response, oxidative stress, apoptosis and hemodynamics in diabetic retina. Tanshinones and luteolin from Radix Salviae were probably responsible for the effectiveness of CDDP on DR.

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Studies on the relationship of binding affinity to psychoactive and anticholinergic potency of a group of psychotomimetic glycolates

Cited by 26 publications

References 15 publications

Quinuclidinyl Benzilate Binding in House Fly Heads and Rat Brain

Quinuclidinyl Benzilate Binding in House Fly Heads and Rat Brain

Muscarinic Receptors of the Pancreas: a Correlation between Displacement of (<sup>3</sup>H)-Quinuclidinyl Benzilate Binding and Amylase Secretion

Therapeutic Opportunities for Muscarinic Receptors in the Central Nervous System

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