Milacemide effects on the temporal inter-relationship of amino acids and monoamine metabolites in rat cerebrospinal fluid.
The temporal inter-relationship of various amino acids and monoamine metabolites in rat cerebrospinal fluid was examined after acute administration of milacemide (100, 200 or 400 mg/kg i.p.), a glycine prodrug. Glycine concentrations rose linearly and dose dependently (20-190%) but were only significantly elevated at the higher milacemide dose (200 and 400 mg/kg). In animals given 400 mg/kg, glycine values were still significantly elevated 8 h later. A concomitant increase (20-25%) in serine and taurine and a decrease in alanine cerebrospinal fluid values were observed at the highest milacemide dose. Other amino acids were unaffected. While cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations were unaffected, the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, exhibited a linear dose-dependent reduction. However, only homovanillic acid values were significantly decreased after 400 mg/kg milacemide. Cerebrospinal fluid analysis may be useful as a first screen in ascertaining putative neurochemical changes associated with drug administration.
Semba
J
J
University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, UK.
Patsalos
P N
PN
D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D000081:Acetamides / Q000494:pharmacology*; D000596:Amino Acids / Q000134:cerebrospinal fluid*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D005998:Glycine / Q000134:cerebrospinal fluid; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000134:cerebrospinal fluid
D000081:Acetamides; D000596:Amino Acids; D000927:Anticonvulsants; D015306:Biogenic Monoamines; C039332:milacemide; D015102:3,4-Dihydroxyphenylacetic Acid; D013654:Taurine; D005998:Glycine; D006719:Homovanillic Acid