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Direct-Acting Cholinergic Agonists: Therapeutic Uses01:11

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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren syndrome.
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A new inotropic aminosteroid: LND 623.

F X Jarreau, J J Koenig, S Fenard

    European Heart Journal
    |December 1, 1984
    PubMed
    Summary
    This summary is machine-generated.

    A novel aminosteroid, LND 623, exhibits potent inotropic effects comparable to digoxin but with a greater maximum contractile force increase. This suggests a re-evaluation of molecular requirements for cardioactive drug interactions.

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    Area of Science:

    • Cardiovascular Pharmacology
    • Medicinal Chemistry
    • Steroid Chemistry

    Background:

    • The 17 beta side chain of cardioactive glycosides is traditionally considered crucial for pharmacological activity.
    • Existing cardioactive steroids like ouabain and digoxin have specific structural requirements for efficacy.

    Purpose of the Study:

    • To synthesize and evaluate a novel aminosteroid, LND 623, lacking typical cardioactive glycoside structural features.
    • To assess the inotropic potential and mechanism of action of LND 623.

    Main Methods:

    • Synthesis of the novel aminosteroid LND 623.
    • In vitro assessment of inotropic effects at various concentrations.
    • Evaluation of LND 623's activity in the presence of propranolol.

    Main Results:

    • LND 623 demonstrated significant inotropic activity at concentrations similar to ouabain and digoxin.
    • The maximum increase in contractile force induced by LND 623 was notably higher than that of reference drugs.
    • The inotropic effect of LND 623 was unaffected by propranolol, suggesting a non-beta-adrenergic mechanism.

    Conclusions:

    • LND 623 possesses potent cardioactive properties despite lacking the canonical 17 beta side chain.
    • The findings challenge the established molecular requirements for interaction with the 'inotropic receptor'.
    • Further investigation into the mechanism of LND 623 is warranted to redefine drug-receptor interactions in cardiac glycoside research.