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Heat Tolerance and the Peripheral Effects of Anticholinergics. 1. A Non-Invasive Method for Estimating the Cholinergic Sensitivity of the Eccrine Glands in Humans.

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Annual rept. 1 Sep 83-31 Aug 84,

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Chubley et al proposed that measurement forearm sweat responses to graded intradermal injections of acetylcholine can be used as a sensitive index of anticholinergic drug potency. A human sweat gland assay has been developed which differs from theirs in several important respects It stimulates larger, well-defined areas it uses non-invasive iontophoresis instead of intradermal injection for administration of mecholyl it is comprehensive, and measures both active gland density and the time course of sweat productions simultaneously on four adjacent test sites instead of only total glands responding and antagonists can be administered to skin sites by iontophoretic pretreatments and their effects on mecholyl dose-response relationships directly measured. By Faradays Law, the total dose of ions delivered to skin is proportional to the product of current density and duration of iontophoresis. This defines the highest possible dose, i.e., the condition in which only drug ions are kept available for transport. In these studies current density and duration were constant at 0.132 mA-sq cm and 180 sec, respectively, and the maximum drug transfer was 250 nMOl-sq cm. Lesser doses are produced with the same current-time combination by diluting drug solutions with equimolar sodium chloride solution The total number of ions transported is always the same but the proportion of drug ions varies. From over 300 individual test replications in more than 35 subjects, we conclude that this essay method can be used safely in normal subjects without peripheral or systemic side effects. Typical mecholyl log dose-response curves are produced for both sweat rate and active gland density over a dose range of 0.4 to 250-sq cm mecholyl.

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  • Pharmacology
  • Stress Physiology

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