Homovanillic acid: Entry rate kinetics for transfer from plasma to cerebrospinal fluid

Because some studies have indicated that 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid [HVA]) does not cross the blood-CSF barrier, it is assumed by some that CSF HVA levels, after L-DOPA administration, validly reflect central nervous system (CNS) metabolism of dopamine. These experiments were designed to test the validity of this assumption. First, it was established that DOPA, administered i.v. to dogs, causes elevations of blood HVA, indicating systemic metabolism of DOPA to the end-product of its metabolic cycle, i.e., HVA. Then, a loading dose and i.v. infusion of HVA were administered to anesthetized dogs to produce a constant blood level for 2–3 h. Serial blood and CSF samples were analyzed fluorometrically for HVA. CSF samples were withdrawn via an indwelling cisternal needle. Entry rates (%/min) were calculated according to Davson 8. In 5 animals, the values were 0.44 ± 0.16 (S.D.). In 2 of these animals, [ 14C]mannitol was administered simultaneously with the HVA. Entry rate for mannitol was calculated in 5 animals and was 0.07 ± 0.04 (S.D.). The diffusion coefficients for HVA and [ 14C]mannitol in agar gel were determined. Values were similar, i.e., 0.76 and 0.41 (× 10 −5) respectively. The data indicate that a significant amount enters CSF at a rate faster than that which would be expected by simple diffusion alone. Therefore, canine CSF HVA levels do not indicate CNS DOPA metabolism alone after systemic DOPA administration. Consequently, CSF HVA levels may not indicate human CNS DOPA metabolism after therapeutic administration.