Carbidopa attenuation of L-DOPA emesis in dogs: evidence for a cerebral site of action outside the blood-brain barrier

L-Dopa and dopamine administered intracerebroventricularly (i.c.vent.) to dogs were approximately 50 times more potent as emetic agents than when administered i.v. The fact that dopamine, which penetrates the CNS only poorly, was more potent than L-dopa by both routes of administration, suggested a central extra-blood-brain barrier site of action for L-dopa-induced emesis. Systemically administered D,L-carbidopa, an inhibitor of aromatic amino acid decarboxylase, did not affect the emetic action of systemically administered dopamine but attenuated the emetic response to L-dopa administered both i.v. or i.c.vent. Since D,L-carbidopa does not penetrate whole brain to a significant extent it was concluded that carbidopa attenuates L-dopa-induced emesis by inhibiting the decarboxylation of L-dopa to dopamine at a CNS site lying outside the blood-brain barrier.