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Chemical Compound Review

Glyzac     2-(pentylamino)ethanamide

Synonyms: Glyzan, Milacemida, Milacemide, Milacemidum, CHEMBL75838, ...
 
 
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Disease relevance of Milacemide

  • These observations suggest that milacemide could enhance dopaminergic activity in the brain and could be used as therapy for Parkinson's disease in association with L-3,4-dihydroxyphenylalanine [1].
  • A therapeutic trial of milacemide in myoclonus and the stiff-person syndrome [2].
  • We performed a therapeutic trial with the glycine precursor, milacemide, on 10 patients with intractable movement disorders [3].
  • These results confirm the existence of an abnormal glial Na+,K(+)-ATPase in cold-induced focal epilepsy and suggest that the antiepileptic activity of milacemide might be secondary to an activation of glial Na+,K(+)-ATPase, contributing to antagonize ictal transformation and seizure spread [4].
  • The results of this study using an in vivo/in vitro approach clearly show potential hepatotoxic properties of Milacemide, an effect not observed in conventional toxicity studies [5].
 

Psychiatry related information on Milacemide

  • The reaction-time functions for milacemide and placebo were similar, suggesting arousal was not diminished under milacemide and could not account for the cognitive decrements [6].
  • Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type [7].
  • Experiment 2 demonstrated that the same dose of milacemide could also attenuate spontaneous forgetting of passive avoidance learning, thereby ruling out nonspecific effects as an explanation for the enhancement of performance following pretesting drug administration [8].
  • Acute and subacute CNS effects of milacemide in elderly people: double-blind, placebo-controlled quantitative EEG and psychometric investigations [9].
 

High impact information on Milacemide

  • Milacemide (100-600 mg/kg, i.v.) dose-dependently inhibited the heart rate and pressor responses (ED50 = 398 mg/kg; 95%CI = 196-873) and the motor responses (ED50 = 404 mg/kg; 95%CI = 275-727) [10].
  • Inactivation of monoamine oxidase B by analogues of the anticonvulsant agent milacemide (2-(n-pentylamino)acetamide) [11].
  • The inhibitory activity of milacemide is significantly greater for MAO-B [1].
  • The apparent Km (30-90 microM) for milacemide oxidation by mitochondrial MAO-B preparations is significantly lower than that for milacemide oxidation by mitochondrial MAO-A (approximately 1,300 microM) [12].
  • In vitro MAO-B (l-deprenyl and AGN 1135) rather than MAO-A (clorgyline) selectively inhibited the oxidation of milacemide [12].
 

Chemical compound and disease context of Milacemide

 

Biological context of Milacemide

  • Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: milacemide [13].
  • Despite our negative findings for milacemide, other strategies for facilitating NMDA-mediated neural transmission in schizophrenia might be worth pursuing [14].
  • Milacemide had a specific inhibitory effect on xenobiotic biotransformation: ECOD activity decreased to 60% of the control value for both Milacemide doses, PROD activity remained unaffected whereas EROD activity decreased to 65% of the control value [5].
  • Because NMDA receptor activation appears involved in induction of long-term potentiation, it was hypothesized that milacemide administration would be involved in task acquisition [15].
  • Milacemide has a low toxicity (LD50: 2585 mg/kg in the mouse) and alters the behaviour of mouse, rat and monkey, only at high doses (greater than or equal to 1000 mg/kg) [16].
 

Anatomical context of Milacemide

 

Associations of Milacemide with other chemical compounds

 

Gene context of Milacemide

 

Analytical, diagnostic and therapeutic context of Milacemide

References

  1. The novel neuropsychotropic agent milacemide is a specific enzyme-activated inhibitor of brain monoamine oxidase B. Janssens de Varebeke, P., Pauwels, G., Buyse, C., David-Remacle, M., De Mey, J., Roba, J., Youdim, M.B. J. Neurochem. (1989) [Pubmed]
  2. A therapeutic trial of milacemide in myoclonus and the stiff-person syndrome. Brown, P., Thompson, P.D., Rothwell, J.C., Day, B.L., Marsden, C.D. Mov. Disord. (1991) [Pubmed]
  3. Therapeutic trial of milacemide in patients with myoclonus and other intractable movement disorders. Gordon, M.F., Diaz-Olivo, R., Hunt, A.L., Fahn, S. Mov. Disord. (1993) [Pubmed]
  4. Milacemide stimulates deficient glial Na+, K(+)-ATPase in freezing-induced epileptogenic cortex of cats. Laschet, J., Guillaume, D., Vergniolle-Burette, M., Grisar, T. Brain Res. (1990) [Pubmed]
  5. Observation of hepatotoxic effects of 2-n-pentylaminoacetamide (Milacemide) in rat liver by a combined in vivo/in vitro approach. Rogiers, V., Vandenberghe, Y., Vanhaecke, T., Geerts, A., Callaerts, A., Carleer, J., Roba, J., Vercruysse, A. Arch. Toxicol. (1997) [Pubmed]
  6. Cognitive effects of milacemide and methylphenidate in healthy young adults. Camp-Bruno, J.A., Herting, R.L. Psychopharmacology (Berl.) (1994) [Pubmed]
  7. Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type. Dysken, M.W., Mendels, J., LeWitt, P., Reisberg, B., Pomara, N., Wood, J., Skare, S., Fakouhi, J.D., Herting, R.L. Journal of the American Geriatrics Society. (1992) [Pubmed]
  8. Milacemide enhances memory storage and alleviates spontaneous forgetting in mice. Quartermain, D., Nuygen, T., Sheu, J., Herting, R.L. Pharmacol. Biochem. Behav. (1991) [Pubmed]
  9. Acute and subacute CNS effects of milacemide in elderly people: double-blind, placebo-controlled quantitative EEG and psychometric investigations. Saletu, B., Grünberger, J., Linzmayer, L. Archives of gerontology and geriatrics. (1986) [Pubmed]
  10. Milacemide, a glycine pro-drug, inhibits strychnine-allodynia without affecting normal nociception in the rat. Khandwala, H., Loomis, C.W. Pain (1998) [Pubmed]
  11. Inactivation of monoamine oxidase B by analogues of the anticonvulsant agent milacemide (2-(n-pentylamino)acetamide). Nishimura, K., Lu, X., Silverman, R.B. J. Med. Chem. (1993) [Pubmed]
  12. Formation of the neurotransmitter glycine from the anticonvulsant milacemide is mediated by brain monoamine oxidase B. Janssens de Varebeke, P., Cavalier, R., David-Remacle, M., Youdim, M.B. J. Neurochem. (1988) [Pubmed]
  13. Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: milacemide. Semba, J., Curzon, G., Patsalos, P.N. Br. J. Pharmacol. (1993) [Pubmed]
  14. An NMDA intervention strategy in schizophrenia with "low-dose" milacemide. Rosse, R.B., Schwartz, B.L., Davis, R.E., Deutsch, S.I. Clinical neuropharmacology. (1991) [Pubmed]
  15. Milacemide treatment in mice enhances acquisition of a Morris-type water maze task. Finkelstein, J.E., Hengemihle, J.M., Ingram, D.K., Petri, H.L. Pharmacol. Biochem. Behav. (1994) [Pubmed]
  16. Anticonvulsant activity of milacemide. van Dorsser, W., Barris, D., Cordi, A., Roba, J. Archives internationales de pharmacodynamie et de thérapie. (1983) [Pubmed]
  17. Effects of the glycine prodrug milacemide (2-N-pentylaminoacetamide) on catecholamine secretion from isolated adrenal medulla chromaffin cells. Yadid, G., Zinder, O., Youdim, M.B. Br. J. Pharmacol. (1991) [Pubmed]
  18. Effect of milacemide, a glycinamide derivative, on the rat brain gamma-aminobutyric acid system. de Varebeke, P.J., Niebes, P., Pauwels, G., Roba, J., Korf, J. Biochem. Pharmacol. (1983) [Pubmed]
  19. Microionophoretic study with milacemide, a glycine precursor, on mammalian central nervous system cells. Godfraind, J.M. Br. J. Pharmacol. (1990) [Pubmed]
  20. A microdialysis study of glycinamide, glycine and other amino acid neurotransmitters in rat frontal cortex and hippocampus after the administration of milacemide, a glycine pro-drug. Doheny, M.H., Nagaki, S., Patsalos, P.N. Naunyn Schmiedebergs Arch. Pharmacol. (1996) [Pubmed]
  21. Species differences in the interactions of the anticonvulsant milacemide and some analogues with monoamine oxidase-B. O'Brien, E.M., Dostert, P., Tipton, K.F. Biochem. Pharmacol. (1995) [Pubmed]
  22. A discontinuous luminometric assay for monoamine oxidase. O'Brien, E.M., Kiely, K.A., Tipton, K.F. Biochem. Pharmacol. (1993) [Pubmed]
  23. Simple and rapid micro-analytical procedures for the estimation of milacemide and its metabolite glycinamide in rat plasma and cerebrospinal fluid by high-performance liquid chromatography. Semba, J., Ratnaraj, N., Patsalos, P.N. J. Chromatogr. (1991) [Pubmed]
  24. Milacemide effects on the temporal inter-relationship of amino acids and monoamine metabolites in rat cerebrospinal fluid. Semba, J., Patsalos, P.N. Eur. J. Pharmacol. (1993) [Pubmed]
  25. Effect of milacemide on extracellular and tissue concentrations of dopamine and 5-hydroxytryptamine in rat frontal cortex. Semba, J., Doheny, M., Patsalos, P.N., Sarna, G., Curzon, G. Br. J. Pharmacol. (1992) [Pubmed]
  26. Double-blind study of milacemide in hospitalized therapy-resistant patients with epilepsy. Houtkooper, M.A., van Oorschot, C.A., Rentmeester, T.W., Höppener, P.J., Onkelinx, C. Epilepsia (1986) [Pubmed]
  27. Milacemide and other drugs active at glutamate NMDA receptors as potential treatment for dementia. Herting, R.L. Ann. N. Y. Acad. Sci. (1991) [Pubmed]
 
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