Psychiatry related information on Amiflamine

• 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 [1].

High impact information on Amiflamine

• Oral doses of 1 to 100 mg amiflamine, a new reversible monoamine oxidase type A-selective inhibitor, were given for the first time in humans to six healthy men [2].
• Tolerance and pilot pharmacokinetics of amiflamine after increasing single oral doses in healthy subjects [2].
• The metabolism of the new reversible A-selective monoamine oxidase inhibitor amiflamine was studied in relation to polymorphic hydroxylation of debrisoquine in 24 healthy subjects [3].
• Increased total activity in the rat after L-tryptophan plus the monoamine oxidase-A inhibitor amiflamine but not after L-tryptophan plus clorgyline [4].
• The effects of amiflamine on cerebrospinal fluid amine metabolites in the rhesus monkey [1].

Biological context of Amiflamine

• Lesioning of serotonergic nerve terminals affected the down-regulation of 5-HT2 binding sites produced by long-term treatment with mianserin, desipramine and amiflamine [5].
• The effects of amiflamine on tyramine deamination were studied using isolated loops of intestine in anesthetized dogs [6].
• The effects of long-term treatment of rats with alaproclate and amiflamine on the number and kinetics of 5-HT1 and 5-HT2 binding sites were investigated using in vitro receptor binding techniques [7].

Anatomical context of Amiflamine

• Selective inhibition by amiflamine of monoamine oxidase type A in rat brain, liver and duodenum [8].
• Ki values, determined at pH 7.2, were 1.3, 0.3 and 22 microM (liver) and 0.8, 0.2 and 14 microM (hypothalamus) for amiflamine, FLA 788(+) and FLA 668(+), respectively [9].
• These two compounds also reversibly and competitively inhibited rat testis MAO-A with FLA 788(+) being much more selective towards this MAO (Kislope = 0.26 mumol/l for FLA 788(+) and 7 mumol/l for amiflamine, respectively) [10].
• The use of selective inhibitors of MAO-A (clorgyline and amiflamine) and MAO-B (deprenyl) showed that MAO-A was localized predominantly in noradrenergic nerve terminals as well as in the cell membrane of endothelial cells [11].

Associations of Amiflamine with other chemical compounds

• It is concluded that in addition to monoamine oxidase-A inhibition, other pharmacological effects of the drugs, such as 5-HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L-tryptophan [4].
• Upon repeated administration of amiflamine the behavioural changes disappeared which indicates a functional down-regulation of the serotonin receptors responsible for this syndrome [12].
• Effects of p-chlorophenylalanine, amiflamine and melatonin treatment on the ultrastructure of pinealocytes in Sus scrofa [13].
• The effect of repeated treatment of rats for 21 days with the monoamine reuptake inhibitors imipramine, zimeldine, alaproclate (in each case 10 mumol/kg b.i.d.) and the reversible monoamine oxidase-A inhibitor amiflamine (3 mumol/kg b.i.d.) on brain noradrenergic mechanisms measured at different times of the day and night was investigated [14].

Gene context of Amiflamine

• Monoamine oxidase-A selective inhibition in human hypothalamus and liver in-vitro by amiflamine and its metabolites [9].
• Ex vivo experiments indicated that there was no significant irreversible inhibition of rat heart and lung SSAO after both single and repeated administration of amiflamine at doses up to 20 times higher than required for inhibition of MAO-A within central serotoninergic neurones [15].
• Inhibition of monoamine oxidase A-form and semicarbazide-sensitive amine oxidase by selective and reversible monoamine oxidase-A inhibitors, amiflamine and FLA 788(+) [10].
• 1. Mice of four ages between newborn and adult were exposed to the monoamine oxidase inhibitor amiflamine both acutely and in an extended (5 day) regimen [16].

Analytical, diagnostic and therapeutic context of Amiflamine

• The in vitro effect of FLA 788(+) was 2-6 times stronger than that of amiflamine although the compounds were equipotent after oral administration [8].

References