Inhibition of respiratory neural discharges by clonidine and 5-hydroxytryptophan

Activation of receptors for norepinephrine or serotonin in the central nervous system by i.v. injection of clonidine (10-50 micrograms/kg) or 5-hydroxytryptophan (20-40 mg/kg) inhibits phrenic neural discharges in anesthetized, artificially ventilated cats. Clonidine induces a rapid and complete inhibition of phrenic nerve activity which lasts for 1 to 3.2 hr. The inhibition is prevented by prior administration of phenoxybenzamine (10 mg/kg) or tolazoline (3 mg/kg). 5-Hydroxytryptophan, injected after inhibition of peripheral amino acid decarboxylase (carbidopa, 30-50 mg/kg), elicits a gradual but complete inhibition of phrenic nerve discharges which persists for 1 to 10 hr and is unaltered by alpha or beta adrenoceptor blocking agents. The inhibitions produced by clonidine and 5-hydroxytryptophan are overcome transiently during hypercapnia. Stimulation of carotid body chemoreceptors by i.a. injections of lobeline, doxapram or 0.015 N HCl in saline also briefly reinstates phrenic nerve discharges after inhibition by clonidine. Inhibition is also overcome during electrical stimulation of the carotid sinus nerve.