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Heat Tolerance and the Peripheral Effects of Anticholinergics

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Annual rept. 1 Dec 1984-31 Dec 1985; Final rept. 1 Sep 1983-31 Dec 1985,

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In clinical studies of anticholinergic efficacy in humans in which either basal level of parasympathetic tone or heat stress is used as a stimulus, it is difficult to estimate potency directly because the acetylcholine ACh level being antagonized is unknown. Clinical studies are further confounded by questions of metabolism, bioavailability, and pharmacokinetics. Direct potencies of cholinergic agonists and antagonists are often determined from in vitro dose-response assays on isolated tissues suspended in organ baths, where the concentration of drugs can be carefully controlled. It would be useful, to supplement findings of conventional clinical studies with data from a direct human assay method that would have the precision of the organ bath but could be used in situ on a sensitive muscarinic and organ. The overall objectives of this study are 1 to develop technology for obtaining accurate and reproducible dose-response data non-invasively from the eccrine sweat gland system, 2 to compare effectiveness of different locally applied cholinergic muscarinic antagonists in altering dose-response patterns of eccrine glands to locally applied cholinergic agonists, 3 to study the time course of changes in cholinergic sensitivity of the eccrine glands during acclimation to heat, and 4 to compare the effect of locally and systematically applied antagonists on responses to locally applied agonist.

Subject Categories:

  • Anatomy and Physiology
  • Stress Physiology
  • Toxicology
  • Pharmacology

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