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Cutaneous responses to anticholinergics: Evidence for muscarinic receptor subtype participation

1991; Elsevier BV; Volume: 87; Issue: 5 Linguagem: Inglês

10.1016/0091-6749(91)90419-o

1097-6825

Diana K. Cavanah, Thomas B. Casale,

Neuropeptides and Animal Physiology

We conducted a series of experiments to determine if anticholinergics induce immediate cutaneous wheal-and-flare responses in normal volunteers.We performed intradermal skin testing in seven healthy volunteers (three atopic and four nonatopic) with 20 nmol of atropine.All subjects had an immediate wheal-and-flare response to atropine.To determine if this cutaneous response was due to anticholinergics in general, skin testing was also performed to scopolamine and ipratropium.These agents also produced immediate wheal-and-flare responses in all subjects, but they less potent than atropine.Pretreatment with antihistamines equivalently inhibited wheal-and-jlare responses to both histamine and atropine, indicating a possible mast cell role.The potential role of MI, M2, and M3 muscarinic receptor subtypes was evaluated by use of the selective antagonists, pirenzepine (Ml), 11(AFDX-I 16) (M2), and 4-diphenylacetoxy-N-methylpiperidine (II-DAMP) (M3).Cutaneous wheal responses induced by pirenzepine and 4-DAMP were relatively equivalent and larger than responses induced by AFDX-116 at doses <200 nmol.At 200 nmol, all three muscarinic receptor subtype antagonists induced equivalent wheal formation.We then compared the cutaneous wheal responses to these specific muscarinic receptor antagonists based on their relative afJinity for their respective muscarinic receptor subtype.This comparison suggested that Ml or M2, but not M3, muscarinic receptor subtypes may be important in anticholinergic-induced cutaneous wheal-and-flare responses.We propose that there may be an Ml or M2 muscarinic autoreceptor that inhibits the release of acetylcholine and other neurotransmitters.Anticholinergic-induced cutaneous wheal-and-flare responses may then result ji-om inhibition of this autoreceptor, thereby allowing release of acetylcholine and other neurotransmitters leading to an immediate wheal-and-flare response.(J ALLERGY CLIN IMMUNOL 1991;87:971-6.)We recently received a consultation requesting evaluation of a patient with possible atropine-induced anaphylaxis.A review of the literature revealed that case reports of atropine hypersensitivity are rare.We did find two case reports of possible allergic reactions to atropine with positive intradermal skin testing to atropine.', 2 However, neither article clearly documented atropine skin testing in control subjects.We therefore Abbreviations used AFDX-116: 1 l-[[2-[(diethylamino)methyl]-lpiperidinyll-acetyll-5,l l-dihydro-6H-pyrido[2,3-b][ 1,4]benzodiazepine-6-one 4-DAMP: 4-Diphenylacetoxy-Nmethylpiperidine