Effects of locally and systemically administered cholinoceptor antagonists on the secretory response of human eccrine sweat glands to carbachol.
Eleven healthy male volunteers participated in a study comparing the effects of locally and systemically administered cholinoceptor antagonists on the secretory response of sweat glands to intradermally injected carbachol chloride. Atropine sulphate administered locally into the skin antagonised the response to carbachol: the dose-response curve for carbachol was shifted to the right without any depression of the maximum of the curve. The nicotinic receptor antagonists hexamethonium bromide and (+)-tubocurarine chloride, however, had little effect on the response to carbachol. Atropine sulphate, administered systemically by intramuscular injection, caused a non-surmountable antagonism of the response to carbachol: the maximum of the dose-response curve was depressed with little change in the value of ED50. Atropine methonitrate (a mixed muscarinic/nicotinic receptor antagonist), and hexamethonium bromide (a nicotinic receptor antagonist), both with poor access to the central nervous system, were injected intramuscularly: both caused non-surmountable antagonism of the response to carbachol. It is concluded that the response to carbachol is mediated by muscarinic rather than nicotinic receptors. The effect of atropine sulphate on the response to carbachol depends on the route of administration: while locally applied atropine sulphate appears to act as a competitive antagonist, systemically applied atropine sulphate, like atropine methonitrate and hexamethonium bromide, appears to act in a non-competitive manner. It is suggested that the systemically administered cholinoceptor antagonists reduce the response to carbachol by interacting with cholinoceptors in sympathetic ganglia: such an interaction would reduce the impulse flow in sudomotor fibres resulting in decreased sensitivity of the sweat glands to carbachol.
Longmore
J
J
Bradshaw
C M
CM
Szabadi
E
E
D000328:Adult; D001285:Atropine / Q000008:administration & dosage; D001286:Atropine Derivatives / Q000008:administration & dosage; D002217:Carbachol / Q000494:pharmacology*; D004439:Eccrine Glands / Q000187:drug effects* / Q000378:metabolism; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000008:administration & dosage; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D013545:Sweat Glands / Q000187:drug effects*; D014403:Tubocurarine / Q000008:administration & dosage
D001286:Atropine Derivatives; D006584:Hexamethonium Compounds; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D001285:Atropine; C006649:methylatropine; D002217:Carbachol; D014403:Tubocurarine