Topical use of anticholinergic drugs could theoretically avoid systemic side effects. However, sufficient absorption through the skin to affect cholinergic nerve endings may be a limiting factor, requiring higher concentrations of drug that may lead to systemic absorption and side effects.[58] Contact sensitization is also possible.[58] Propantheline, scopolamine, and poldine methylsulfate are among the anticholinergics used experimentally for hyperhidrosis.[58] Topical propantheline delivered by aerosol was effective in decreasing plantar sweating in institutionalized patients.[37] Poldine methosulfate and glycopyrronium bromide were delivered via iontophoresis in two different studies, with some reduction in palmoplantar symptoms.[1,47] Axillary hyperhidrosis did not respond as well, and systemic side effects were noted in many patients, particularly when higher doses were used.[1,47]

Topical glycopyrrolate in 0.5% cream was used to treat gustatory hyperhidrosis in a series of patients with diabetes.[128] Compared to placebo, glycopyrrolate cream reduced forehead hyperhidrosis during gustatory challenge by 82% (P<0.01).[128] The frequency of episodes of gustatory sweating significantly decreased during the period of active treatment.[128] Glycopyrrolate is a quaternary ammonium anticholinergic with limited central nervous system effects and higher anticholinergic potency compared to atropine or scopolamine.[92] In a single case report, a 0.5% topical solution of glycopyrrolate effectively relieved primary craniofacial hyperhidrosis.[92]

Another anticholinergic agent, diphemanil methylsulfate, was used successfully in 15 patients with Frey�s syndrome.[81] Compared to placebo, 2% diphemanil methylsulfate cream provided partial symptom reduction in a third of patients and complete reduction in 40% of patients. The effect lasted two to four days, and two patients reported a dryness of the mouth, suggesting some systemic absorption.

Peripheral nerve blockade by use of local anesthetics could also lead to anhidrosis by blocking sympathetic nerve transmission to eccrine sweat glands.[58] Although a eutectic mixture of 5% lidocaine and 5% prilocaine reduced palmar and axillary hyperhidrosis in 15 of 17 patients for up to six hours, when used daily for three to four weeks, only 25% of the patients were satisfied with the therapy.[2,3,6,75]