Abstract
The location of probenecid-sensitive elimination mechanisms of monoamine metabolites from the cerebrospinal fluid of the cat was determined with ventriculo-cisternal or ventriculo-lumbar perfusion techniques. These techniques were described in detail. Levels of endogenous homovanillic acid and 5-hydroxyindoleacetic acid were assayed in the perfusate. Probenecid administration induced the most marked increase of the levels of the monoamine metabolites in the ventriculo-lumbar perfusates. It was concluded that probenecid blocked the transport of both metabolites from the spinal subarachnoid space.
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Ashcroft, G. W., Dow, R. C., Moir, A. T. B.: The active transport of 5-hydroxyindol-3-ylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid from a recirculatory perfusion system of the cerebral ventricles of the un-anaesthetized dog. J. Physiol. (Lond.) 199, 397–425 (1968)
Bowers, J. B., Jr.: 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) following probenecid in acute psychotic patients, treated with phenothiazines. Psychopharmacologia (Berl.) 28, 309–318 (1973)
Bulat, M., Živković, B.: Penetration of 5-hydroxyindoleacetic acid across the blood-cerebrospinal fluid barrier. J. Pharm. Pharmacol. 25, 178–179 (1973)
Curzon, G., Gompert, E. J. W., Sharpe, D. M.: Amine metabolites in the lumbar cerebrospinal fluid of humans with restricted flow of cerebrospinal fluid. Nature New Biol. 231, 189–191 (1971)
Garelis, E., Young, S. N., Lal, S., Sourkes, T. L.: Monoamine metabolites in lumbar CSF: the question of their origin in relation to clinical studies. Brain. Res. 79, 1–8 (1974)
Gerbode, F. A., Bowers, M. B., Jr.: Measurement of acid monoamine metabolites in human and animal cerebrospinal fluid. J. Neurochem. 15, 1053–1055 (1968)
Guldberg, H. C., Ashcroft, G. W., Crawford, T. B. B.: Concentrations of 5-hydroxyindoleacetic acid and homovanillic acid in the cerebrospinal fluid of the dog before and during treatment with probenecid. Life Sci. 5, 1571–1575 (1966)
Kessler, J. A., Feustermacher, J. D., Patlak, C. S.: Homovanillic acid transport by the spinal cord. Neurology (Minneap.) 26, 434–440 (1976a)
Kessler, J. A., Gordon, E. K., Reid, J. L., Kopin, I. J.: Homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol production by the monkey spinal cord. J. Neurochem. 26, 1057–1061 (1976b)
Korf, J., van Praag, H. M.: Amine metabolites in the human brain: Further evaluation of the probenecid test. Brain Res. 35, 221–230 (1971)
Korf, J., Schutte, H. H., Venema, K.: A semi-automated fluorometric determination of 5-hydroxyindoles in the nanogram range. Analyt. Biochem. 53, 146–153 (1973)
Neff, N. H., Tozer, T. N., Brodie, B. B.: Application of steady-state kinetics to studies of the transfer of 5-hydroxyindoleacetic acid from brain to plasma. J. Pharmacol. exp. Ther. 158, 214–218 (1967)
Post, R. M., Goodwin, F. K.: Effects of amitriptyline and imipramine on amine metabolites in the cerebrospinal fluid of depressed patients. Arch. gen. Psychiat. 30, 234–239 (1974)
Roos, B.-E.: On the occurrence and distribution of 5-hydroxy-indoleacetic acid in brain. Life Sci. 1, 25–27 (1962)
Sampath, S. S., Neff, N. H.: The elimination of 5-hydroxyindoleacetic acid from cerebrospinal fluid; Characteristics of the acid transport system of the choroid plexus. J. Pharmacol. exp. Ther. 188, 410–414 (1974)
Snider, R. S., Niemer, W. T.: A steeotaxic atlas of the cat brain. Chicago: University of Chicago Press 1961
Van Praag, H. M., Korf, J., Lakke, J. P. W. F., Schut, T.: Dopamine metabolism in depressions, psychosis and Parkinson's disease: the problem of the specificity of biological variables in behaviour disorders. Psychol. Med. 5, 138–146 (1975)
Weir, R. L., Chase, T. N., Ng, L. K., Kopin, I. J.: 5-Hydroxyindoleacetic acid in spinal fluid: a relative contribution from brain and spinal cord. Brain Res. 52, 409–412 (1973)
Westerink, B. H. C., Korf, J.: Determination of nanogram amounts of homovanillic acid in the central nervous system with a rapid semiautomated fluorometric method. Biochem. Med. 12, 106–115 (1975)
Wolfson, L. I., Katzman, R., Escriva, A.: Clearance of amine metabolites from the cerebrospinal fluid: the brain as a “sink”. Neurology (Minneap.) 24, 772–779 (1974)
Young, S. N., Lal, S., Martin, J. B., Ford, R. M., Sourkes, T. L.: 5-Hydroxyindoleacetic acid, homovanillic acid and tryptophan levels in CSF above and below a complete block of CSF flow. Psychiat. Neurol. Neurochir. (Amst.) 76, 439–444 (1973)
Živković, B., Bulat, M.: Inhibition of 5-hydroxyindoleacetic acid transport from the spinal fluid by probenecid. J. Pharm. Pharmacol. 23, 539 (1971)
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Van Der Poel, F.W., Van Praag, H.M. & Korf, J. Evidence for a probenecid-sensitive transport system of acid monoamine metabolites from the spinal subarachnoid space. Psychopharmacology 52, 35–40 (1977). https://doi.org/10.1007/BF00426597
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DOI: https://doi.org/10.1007/BF00426597