Tachyphylaxis to the hypotensive effect of clonidine and the possible mechanism of this action.
In cats under chloralose-urethan anaesthesia, tachyphylaxis developed to the hypotensive effect of clonidine. Development of this tachyphylaxis was slow in the case of intravenous low doses (10--20 micrograms/kg) and rapid after high doses (50 micrograms/kg). No tachyphylaxis developed to contractions of the nictitating membrane. The phenomenon resembles the tachyphyaxis seen after the application of indirect sympathomimetics. A tachyphylaxis developed to the latter agents inhibited the hypotensive action of clonidine which, after such an intervention, invariably turned into a vasopressor effect. Clonidine exhibited the same behaviour after pretreatment with cocaine, bretylium or reserpine. Infusion of noradrenaline (10 micrograms/kg/min) counteracted the tachyphylaxis. Thus, clonidine is assumed to exert its hypotensive effect in an indirect way, i.e. by interference with the metabolism of noradrenaline.
D000661:Amphetamine / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001950:Bretylium Tosylate / Q000008:administration & dosage; D002415:Cats; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004809:Ephedrine / Q000008:administration & dosage; D009638:Norepinephrine / Q000008:administration & dosage; D012110:Reserpine / Q000008:administration & dosage; D013618:Tachyphylaxis; D014439:Tyramine / Q000008:administration & dosage
D001950:Bretylium Tosylate; D012110:Reserpine; D000661:Amphetamine; D004809:Ephedrine; D003042:Cocaine; D003000:Clonidine; D009638:Norepinephrine; D014439:Tyramine