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  • Title: The effects of amiflamine on cerebrospinal fluid amine metabolites in the rhesus monkey.
    Author: Garrick NA, Seppala T, Linnoila M, Murphy DL.
    Journal: Eur J Pharmacol; 1985 Mar 26; 110(1):1-9. PubMed ID: 2408906.
    Abstract:
    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.
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