Skip to main content
SpringerLink
Log in

Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The effects ofd-Met2, Pro5-enkephalinamide (EA) on pain tolerance and some cognitive functions have been examined in healthy male volunteers. Dihydrocodeine (DC) was used as reference substance. Applying the submaximum effort tourniquet technique EA (10 mg SC) was found to elevate the pain threshold similarly to DC (20 mg SC). Neither DC nor EA impaired the performance in the symbol cancellation test, which quantitates the intensity of attention. In this assay rather a slight improvement was detected. In addition the short-term memory performance (Wechsler test) was also improved by EA and DC. No alteration was seen in the word fluency test, an indicator of long-term (semantic) memory. The data show that EA not only improves pain tolerance but some of its mental effects are similar to those of a classical morphine congener DC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Allolio B, Winkelmann W, Hipp FX, Kaulen D, Mies R (1982) Effects of a Met-enkephalin analogue on adrenocorticotropin (ACTH), growth hormone, and prolactin in patients with ACTH hypersecretion. J Clin Endocrinol Metab 55: 1–7

    Article  CAS  PubMed  Google Scholar 

  • Andersen HB, Jørgensen BC, Enquist A (1982) Epidural Met-enkephalin (FK 33-824). A dose effect study. Acta Anaesth Scand 26:69–71

    Article  CAS  PubMed  Google Scholar 

  • Bajusz S, Rónai AZ, Székely JI, Gráf L, Dunai-Kovács Z, Berzétei I (1977) A superactive antinociceptive pentapeptide, (d-Met2, Pro5)-enkephalinamide. FEBS Lett 76: 91–92

    Article  CAS  PubMed  Google Scholar 

  • Bloomfield SS, Barden TP, Mitchell J (1983) Metkephamid and meperidine analgesia after episiotomy. Clin Pharmacol Ther 34: 240–247

    Article  CAS  PubMed  Google Scholar 

  • Brownell J, del Pozo E, Donatsch P (1980) Inhibition of vasopressin secretion by Met-enkephalin (FK 33-824) in humans. Acta Endocrinol 84: 304–308

    Google Scholar 

  • Calimlim JF, Wardell WM, Sriwatanakul K, Lasagna L, Cox C (1982) Analgesic efficacy of parenteral metkephamid acetate in treatment of postoperative pain. Lancet i: 1374–1375

    Article  Google Scholar 

  • Catlin DH, George R, Li CH (1977a) β-endorphin: pharmacologic and behavioural activity in cats after low intravenous doses. Life Sci 23: 2147–2153

    Article  Google Scholar 

  • Catlin DH, Hui KK, Loh HH, Li CH (1977b) Pharmacologic activity of β-endorphin in man. Commun Psychopharmacol 1: 439–442

    Google Scholar 

  • Földes J, Török K, Székely JI, Borvendég J, Karczag I, Tolna J, Marosfi S, Váradi A, Gara Á, Rónai AZ, Szilágyi G (1983) Human tolerability studies withd-Met2, Pro5-enkephalinamide. Life Sci 33: 769–772

    Article  PubMed  Google Scholar 

  • Frederickson RCA, Smithwick EL, Shuman R, Bemis KG (1981) Metkephamid, a systemically active analogue of methionine enkephalin with potent opioid δ-receptor activity. Science 211: 603–605

    CAS  PubMed  Google Scholar 

  • Gaillard RC, Grossman A, Smith R, Rees LH, Besser GM (1981) The effects of a Met-enkephalin analogue on ACTH, β-LPH, β-endorphin and Met-enkephalin in patients with adrenocortical disease. Clin Endocrinol 14: 471–476

    CAS  Google Scholar 

  • Guilford JP (1967) The nature of human intelligence. McGraw-Hill Book Company, New York, pp 138–170

    Google Scholar 

  • Guillemin H, Vargo T, Rossier J, Minick S, Ling N, Rivier C, Vale W, Bloom F (1977) β-endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197: 1367–1369

    CAS  PubMed  Google Scholar 

  • Jørgensen A, Fog H, Veilis B (1979) Synthetic enkephalin analogue in treatment of schizophrenia. Lancet i: 955

    Google Scholar 

  • Katakami H, Kato Y, Matsushita N, Hiroto S, Shimatsu A, Imura H (1981) Involvement of alpha-adrenergic mechanisms in growth hormone release induced by opioid peptides in conscious rats. Neuroendocrinology 33: 129–135

    CAS  PubMed  Google Scholar 

  • Krebs E, Roubicek J (1979) EEG and clinical profile of a synthetic analogue of methionine-enkephalin — FK 33-824. Pharmakopsychiatr Neuro-Psychopharmakol 12: 86–93

    CAS  Google Scholar 

  • Le Toulouse D, VAschide N, Piéron H (1904) Technique de psychologie expérimentale Octave Doin, Paris, pp 177–185

    Google Scholar 

  • Liljequist R (1981) Codeine-induced memory changes: nature and relationship to opiate system. Eur J Clin Pharmacol 20: 99–107

    Article  CAS  PubMed  Google Scholar 

  • Mondadori C, Waser PG (1978) Improvement of retention by posttrial morphine. Experientia 34: 902

    Google Scholar 

  • Nedopil N, Rüther E (1979) Effects of the synthetic analogue of methionine enkephalin FK 33-824 on psychotic symptoms. Pharmakopsychiatr Neuro-Psychopharmakol 12: 277–280

    CAS  Google Scholar 

  • Oleson DS, Zubek JP (1970) Effect of one day of sensory deprivation on a battery of open-ended cognitive tests. Perceptual Motor Skills 31: 919–923

    CAS  Google Scholar 

  • Olive H (1972) A note on sex differences in adolescents' divergent thinking. J Psychol 82: 39–42

    Google Scholar 

  • Oyama T, Jin T, Yamaya R, Ling R, Guillemin R (1980a) Profound analgesic effect of β-endorphin in man. Lancet i: 122–124

    Article  Google Scholar 

  • Oyama T, Matsuki A, Taneichi T, Ling N, Guillemin R (1980b) β-endorphin in obstetric analgesia. Am J Obstet Gynecol 137: 613–617

    CAS  PubMed  Google Scholar 

  • Peñalva A, Villanueva L, Casanueva F, Cavagnini F, Gomez-Pan A, Müller EE (1983) Cholinergic and histaminergic involvement in the growth hormone releasing effect of an enkephalin analogue FK 33-824 in man. Psychopharmacology 80: 120–124

    Article  PubMed  Google Scholar 

  • Rapaport SI, Klee WA, Pettigrew KD, Ohno K (1980) Entry of opioid peptides into the central nervous system. Science 207: 84–86

    Google Scholar 

  • Römer D, Büscher HH, Hill RC, Pless J, Bauer W, Cardinaux F, Closse A, Hauser D, Huguenin R (1977) A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity. Nature 268: 547–549

    Article  Google Scholar 

  • Scott J, Huskisson EC (1976) Graphic representation of pain. Pain 2: 175–184

    Article  CAS  PubMed  Google Scholar 

  • Smith GM, Egbert LD, Markowitz RA, Mosteller F, Beecher HK (1966) An experimental pain method sensitive to morphine in man: the submaximum effort tourniquet technique. J Pharmacol Exp Ther 154: 324–332

    CAS  PubMed  Google Scholar 

  • Stacher G, Bauer P, Steinberger H, Schreiber E, Schmierer G (1979) Effects of the synthetic enkephalin analogue FK 33-824 on pain threshold and pain tolerance in man. Pain 7: 159–172

    Article  CAS  PubMed  Google Scholar 

  • Stubbs WA, Delitala G, Jones A, Jeffcoate WJ, Edwards CRW, Ratter SJ, Besser GM, Bloom SR, Alberti KGMM (1978) Hormonal and metabolic responses to an enkephalin analogue in normal man. Lancet ii: 1225–1227

    Article  Google Scholar 

  • Székely JI (1982) Effects of opiates on conditioned behaviour. In: Székely JI, Rónai AZ Opioid peptides, vol I, chap 2/VIII, CRC Press, Boca Raton, Florida, pp 73–74

    Google Scholar 

  • Székely JI, Rónai AZ, Dunai-Kovács Z, Miglécz E, Berzétei I, Bajusz S, Gráf L (1977) (d-Met2, Pro5)-enkephalinamide: a potent morphine-like analgesic. Eur J Pharmacol 43: 293–294

    Article  PubMed  Google Scholar 

  • Von Graffenried B, del Pozo E, Roubicek J, Krebs E, Poldinger W, Burmeister P, Kerp L (1978) Effects of the synthetic enkephalin analogue FK 33-824 in man. Nature 272: 729–731

    Article  Google Scholar 

  • Wechsler D, (1955) Manual for the Wechsler Adult Intelligence Scale. Psychological Corporation, New York, pp 43–44

    Google Scholar 

  • Weingartner H, Kaye W, Gold P, Smallberg S, Peterson R, Gillin JC, Ebert M (1981) Vasopressin treatment of cognitive dysfunction in progressive dementia. Life Sci 29: 2721–2726

    Article  CAS  PubMed  Google Scholar 

  • White N, Major R, Siegel J (1978) Effects of morphine on one-trial appetitive learning. Life Sci 23: 1967–1972

    Article  CAS  PubMed  Google Scholar 

  • Woods JH, Herling S, Young AM (1981) Comparison of discriminative and reinforcing stimulus characteristics of morphine-like opioids and two met-enkephalin analogues. Neuropeptides 1: 409–419

    Article  CAS  Google Scholar 

  • Zerbe RL, Henry DP, Robertson GL (1982) A new Met-enkephalin analogue suppresses plasma vasopressin in man. Peptides 1: 199–201

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Drug Research, POB 82, H-1325, Budapest, Hungary

    J. I. Székely, Katalin Török & Mária Till

  2. Department of Psychiatry, Semmelweis University Medical School, Balassa u. 6., H-1083, Budapest, Hungary

    I. Karczag & Judit Tolna

Authors
  1. J. I. Székely
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katalin Török
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Karczag
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Judit Tolna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mária Till
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Székely, J.I., Török, K., Karczag, I. et al. Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man. Psychopharmacology 89, 409–413 (1986). https://doi.org/10.1007/BF02412112

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02412112

Key words

Search

Navigation