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Chemical Compound Review

CHEMBL2028951     (4S)-4-[[(2S)-2-amino-4- methylsulfanyl...

Synonyms: ACTH 4-10, AC1L3XAG, LS-72727, ACTH (4-10), AR-1J3351, ...
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Disease relevance of Met-glu-his-phe-arg-trp-gly


Psychiatry related information on Met-glu-his-phe-arg-trp-gly

  • The subjects injected with ACTH 4-10 showed a larger improvement in reaction time during the experimental session than the placebo group [6].
  • These results suggest that ACTH 4-10 has no effect on skill acquisition, but counteracts the build-up of reactive inhibition during the experimental session; that is, the peptide suppresses the decrease in motivation, which usually occurs during continuous performance tasks [6].
  • It was concluded that ACTH 4-10 counteracts the usual decay in performance as a function of time-on-task due to increasing boredom and mental fatigue [6].
  • Subcutaneously injected beta-LPH 61-69 or intraventricularly administered beta-endorphin induced a shift from lower to higher frequencies of hippocampal theta rhythm during paradoxical sleep in the same way as that found after ACTH 4-10 [7].
  • Comparative effects of the ACTH 4-9 analogue (ORG 2766), ACTH 4-10 and [D-Phe7] ACTH 4-10 on medial septal self-stimulation behaviour in rats [8].

High impact information on Met-glu-his-phe-arg-trp-gly

  • Potent neurotrophic fragments are ACTH 4-10, an analog of ACTH 4-9 (Org 2766), and alpha-MSH (ACTH 1-13), peptide fragments that do not evoke corticosteroid secretion, yet clearly affect both the development and regeneration of peripheral nerve [9].
  • (2) Early postnatal administration of either ACTH 4-10 or Org 2766 accelerates the neuromuscular development of the immature rat, increasing the contractile strength of the EDL muscle and inducing more rapid muscle contractions [9].
  • The increase in ERP slow-wave positivity, in conjunction with behavioral impairments after treatment with ACTH 4-10, complemented previous results of inferior focusing of attention and a less concise structure of thought after administration of ACTH 4-10 [10].
  • Short peptide sequences of ACTH 1-39 (the ACTH 4-9 analog Org 2766, ACTH 4-10 and its analog BIM 22015, and ACTH 1-13 [alpha-MSH]), which do not stimulate the adrenal cortex, have profound effects on the developing and regenerating neuromuscular system, in neonatal and in adult rats [11].
  • We tested [Ala6]ACTH(4-10) and [Phe-I7]ACTH(4-10)(putative MC receptor antagonists), [D-Ala4,Gln5,Tyr6]ACTH(4-10)(BIM 22015), and ACTH (4-10) with radioligand binding using transiently expressed human MC1, MC3, MC4, and MC3 receptors [12].

Chemical compound and disease context of Met-glu-his-phe-arg-trp-gly


Biological context of Met-glu-his-phe-arg-trp-gly


Anatomical context of Met-glu-his-phe-arg-trp-gly


Associations of Met-glu-his-phe-arg-trp-gly with other chemical compounds


Gene context of Met-glu-his-phe-arg-trp-gly

  • The order of potency of a number of substance competing for the [125I][Nle4, D-Phe7] alpha-MSH binding was the following; [Nle4, D-Phe7] alpha-MSH > [Nle4]-alpha-MSH > beta-MSH > desacetyl-alpha-MSH > alpha-MSH > ACTH (1-39) > ACTH (4-10) > gamma 1-MSH > gamma 2-MSH [25].
  • Similar treatment with ACTH 4-10 or ACTH 1-24 increased striatal tyrosine hydroxylase activity measured in vitro, but did not significantly alter the enzyme activity from other brain regions [22].
  • Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat [26].
  • Effects of ACTH 4-10 on the AEPs to inattended stimuli, however, differed from influences of the synthetic analog in that they did not affect a rather wide latency range but concentrated on the latency range of the P200 component [27].
  • Arginine vasopressin, but not ACTH 4-10, prolonged the retention of morphine tolerance when assessed five weeks after the last injection [28].

Analytical, diagnostic and therapeutic context of Met-glu-his-phe-arg-trp-gly

  • After a single (1 mg) as well as prolonged intranasal administration (1 mg/day over a period of 6 weeks), ACTH 4-10 enhanced the positive slow wave in ERPs to target stimuli of the vigilance task (p < 0.05), but left classic P3 unaffected [10].
  • ACTH 4-10 enhanced dimensional complexity of the EEG [29].
  • Double-blind studies of ACTH 4-10 and placebo were conducted in psychiatric patients receiving bilateral ECT to determine whether the polypeptide exerted anti-amnesic effects [30].
  • Hypophysectomy results in markedly deleterious changes in neuromuscular function which can be partially alleviated by the administration of ACTH 4-10 (0.01 microgram/kg) [15].
  • A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed [5].


  1. Novel synthetic analogue of ACTH 4-10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia. Bashkatova, V.G., Koshelev, V.B., Fadyukova, O.E., Alexeev, A.A., Vanin, A.F., Rayevsky, K.S., Ashmarin, I.P., Armstrong, D.M. Brain Res. (2001) [Pubmed]
  2. ACTH neuromodulation of the developing motor system and neonatal learning in the rat. Acker, G.R., Berran, J., Strand, F.L. Peptides (1985) [Pubmed]
  3. Effect of ACTH 4-10 on passive avoidance of rats lacking vasopressin (Brattleboro strain). Bailey, W.H., Weiss, J.M. Hormones and behavior. (1978) [Pubmed]
  4. Stimulation of the adenylate cyclase of A B16 melanoma cell line by pro-opiocortin-related peptides--a structure-activity study. Mac Neil, S., Johnson, S.K., Bleehen, S.S., Brown, B.L., Tomlinson, S. Regul. Pept. (1981) [Pubmed]
  5. The behaviorally active peptide ACTH 4-10: measurement in plasma and pharmacokinetics in man. Bickel, U., Born, J., Fehm, H.L., Distler, M., Voigt, K.H. Eur. J. Clin. Pharmacol. (1988) [Pubmed]
  6. Some effects of ACTH 4-10 on performance during a serial reaction task. Gaillard, A.W., Sanders, A.F. Psychopharmacologia. (1975) [Pubmed]
  7. Behavioral and electrophysiological effects of peptides related to lipotropin (beta-LPH). de Wied, D., Bohus, B., van Ree, J.M., Urban, I. J. Pharmacol. Exp. Ther. (1978) [Pubmed]
  8. Comparative effects of the ACTH 4-9 analogue (ORG 2766), ACTH 4-10 and [D-Phe7] ACTH 4-10 on medial septal self-stimulation behaviour in rats. Fekete, M., Bohus, B., Van Wolfswinkel, L., Van Ree, J.M., De Wied, D. Neuropharmacology (1982) [Pubmed]
  9. ACTH modulation of nerve development and regeneration. Strand, F.L., Rose, K.J., King, J.A., Segarra, A.C., Zuccarelli, L.A. Prog. Neurobiol. (1989) [Pubmed]
  10. Event-related brain potentials and working memory function in healthy humans after single-dose and prolonged intranasal administration of adrenocorticotropin 4-10 and desacetyl-alpha-melanocyte stimulating hormone. Smolnik, R., Perras, B., Molle, M., Fehm, H.L., Born, J. Journal of clinical psychopharmacology. (2000) [Pubmed]
  11. Non-corticotropic ACTH peptides modulate nerve development and regeneration. Strand, F.L., Lee, S.J., Lee, T.S., Zuccarelli, L.A., Antonawich, F.J., Kume, J., Williams, K.A. Reviews in the neurosciences. (1993) [Pubmed]
  12. Selectivity of [Phe-I7], [Ala6], and [D-Ala4,Gln5,Tyr6] substituted ACTH(4-10) analogues for the melanocortin receptors. Schiöth, H.B., Muceniece, R., Wikberg, J.E. Peptides (1997) [Pubmed]
  13. The effect of MSH/ACTH 4-10 on delayed response performance and post-test locomotor activity in rats. Miller, L.H., Turnbull, B.A. Peptides (1986) [Pubmed]
  14. Fragments of ACTH affect electrophysiological signs of controlled stimulus processing in humans. Born, J., Kern, W., Pietrowsky, R., Sittig, W., Fehm, H.L. Psychopharmacology (Berl.) (1989) [Pubmed]
  15. Neurotropic action of MSH/ACTH 4-10 on neuromuscular function in hypophysectomized rats. Gonzalez, E.R., Strand, F.L. Peptides (1981) [Pubmed]
  16. Intracranial administration of corticotropin-like peptides increases incidence of amphibian reproductive behavior. Miller, L.J., Moore, F.L. Peptides (1983) [Pubmed]
  17. Adrenocorticotropin widens the focus of attention in humans. A nonliner electroencephalographic analysis. Mölle, M., Albrecht, C., Marshall, L., Fehm, H.L., Born, J. Psychosomatic medicine. (1997) [Pubmed]
  18. ACTH (4-10) increases quantal content at the mouse neuromuscular junction. Davies, D.A., Smith, M.E. Brain Res. (1994) [Pubmed]
  19. Effects of MSH/ACTH 4-10 on the classically-conditioned rabbit nictitating membrane. Schaeffer, C.A., Nathanson, D.C., Cegavske, C.F., Roemer, R.A. Peptides (1982) [Pubmed]
  20. The influence of neuropeptides related to pro-opiomelanocortin on acquisition of heroin self-administration of rats. van Ree, J.M. Life Sci. (1983) [Pubmed]
  21. Dorsal hippocampus: a site of action of neuropeptides on avoidance behavior? Greidanus, T.B., De Wied, D. Pharmacol. Biochem. Behav. (1976) [Pubmed]
  22. Neurochemical responses of mice to ACTH and lysine vasopressin. Dunn, A.J., Iuvone, P.M., Rees, H.D. Pharmacol. Biochem. Behav. (1976) [Pubmed]
  23. Effects of arginine-vasopressin and ACTH 4-10 on acquisition of active avoidance response in rats with alcohol pretreatment in prenatal and adult age. Markel, E., Scaccianoce, S., Korányi, L., Endröczi, E. Acta physiologica Hungarica. (1986) [Pubmed]
  24. Effects of corticotropin releasing hormone on human brain function: an analysis based on auditory evoked potentials. Fehm, H.L., Born, J. Horm. Metab. Res. Suppl. (1987) [Pubmed]
  25. Characterisation of the melanocortin 4 receptor by radioligand binding. Schiöth, H.B., Muceniece, R., Wikberg, J.E. Pharmacol. Toxicol. (1996) [Pubmed]
  26. Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides. Bissette, G., Nemeroff, C.B., Loosen, P.T., Prange, A.J., Lipton, M.A. Pharmacol. Biochem. Behav. (1976) [Pubmed]
  27. Influences of ACTH 4-10 on event-related potentials reflecting attention in man. Born, J., Fehm-Wolfsdorf, G., Voigt, K.H., Fehm, H.L. Physiol. Behav. (1987) [Pubmed]
  28. Arginine vasopressin enhances retention of morphine tolerance. Moore, J.E. Pharmacol. Biochem. Behav. (1983) [Pubmed]
  29. Regulation of human thought by neuropeptide ACTH 4-10: an analysis of the EEG's dimensional complexity. Mölle, M., Pietrowsky, R., Fehm, H.L., Born, J. Neuroreport (1997) [Pubmed]
  30. Effects of ACTH 4-10 on ECT-induced memory dysfunctions. Small, J.G., Small, I.F., Milstein, V., Dian, D.A. Acta psychiatrica Scandinavica. (1977) [Pubmed]
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