Clearance of 3-methoxy-4-hydroxyphenylglycol from the cerebrospinal fluid

The clearance of 3-methoxy-4-hydroxyphenylglycol (MHPG) from the cerebrospinal fluid of cats was studied. Both ventriculocisternal and cerebral subarachnoid perfusions demonstrated relatively high clearances that could not be blocked by probenecid. MHPG removal increased proportionally at all concentrations studied, suggesting diffusional clearance from cerebrospinal fluid. Bulk clearance accounted for only one-third of MHPG clearance from brain, and the likely mechanism of MHPG removal from the central nervous system is by diffusion to capillary blood. Differences between amine metabolites removed by mediated transport and diffusion are summarized, and it is suggested that a rapid unblockable diffusional clearance mechanism tends to make lumbar levels of MHPG a poor index of brain norepinephrine metabolism.