The effects of amiflamine on cerebrospinal fluid amine metabolites in the rhesus monkey.
Amiflamine, a drug reported to be a reversible inhibitor of monoamine oxidase type A (MAO-A) selective for serotonergic neurons in rodents, was administered to rhesus monkeys over a 12-fold dosage range (0.5-6 mg/kg). Amiflamine produced small, essentially equivalent reductions in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA, 1-28%), 3-methoxy-4-hydroxyphenylglycol (MHPG, 4-26%), and homovanillic acid (HVA, 7-29%), suggesting that the effects of amiflamine are approximately equal on serotonin, norepinephrine and dopamine metabolism in nonhuman primates. Concentrations of amiflamine were very low in CSF 3-6 h after drug administration (less than 7 nmol/l), while those of its two major, biologically active metabolites were higher (22-150 nmol/l) and varied in relative proportions among the monkeys. Further investigation is required of some preliminary observations of a possible association between drug metabolite variations and the substantial individual differences in the amine metabolite changes following amiflamine treatment. MAO-B in platelets was not inhibited by 6 mg/kg amiflamine, indicating that MAO-A selectivity was maintained. At low amiflamine doses, early and transient increases in CSF 5-HIAA and HVA concentrations were observed, suggesting an amine-releasing effect of the drug within brain serotonergic and dopaminergic neurons.
Garrick
N A
NA
Seppala
T
T
Linnoila
M
M
Murphy
D L
DL
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006018:Glycols / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008253:Macaca mulatta; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D010648:Phenylacetates / Q000134:cerebrospinal fluid*; D013045:Species Specificity
D006018:Glycols; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D010648:Phenylacetates; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D003010:Clorgyline; C031466:amiflamine; D006719:Homovanillic Acid