Cellular and Molecular Pharmacology

Structural comparisons of meptazinol with opioid analgesics

Abstract

Aim:

To investigate the mechanism of action of a potent analgesic, (±)-Meptazinol.

Methods:

The structure of meptazinol enantiomers were compared with opioid pharmacophore and tramadol.

Results:

Neither enantionmer of meptazional fitted any patterns among the opioid pharmacophore and tramadol, although they did share some structural and pharmacological similarities. However, the structure superpositions implied that both enantiomers of meptazinol might share some similar analgesic mechanisms with typical opiate analgesics.

Conclusion:

Meptazionol should have a different mechanism of action to known analgesics, which would be helpful in further investigations of meptazional in the search for non-addictive analgesics.

References

  1. 1

    Great Britain Medicines Commission . British Pharmacopoeia. London: Bernan Association; 1998. p 859.

  2. 2

    Hoskin PJ, Hanks GW . Opioid agonist-antagonist drugs in acute and chronic pain states. Drugs 1991; 41: 326–44.

    CAS  Article  Google Scholar 

  3. 3

    Green D . Current concepts concerning the mode of action of meptazinol as an analgesic. Postgrad Med J 1983; 59 ( Suppl 1): 9–12.

    CAS  PubMed  Google Scholar 

  4. 4

    Spiegel K, Pasternak GW . Meptazinol: a novel Mu-1 selective opioid analgesic. J Pharmacol Exp Ther 1984; 228: 414B.

    Google Scholar 

  5. 5

    Goode PG, Rhodes KF, Waterfall JF . The analgesic and respiratory effects of meptazinol, morphine and pentazocine in the rat. J Pharm Pharmacol 1979; 31: 793–5.

    CAS  Article  Google Scholar 

  6. 6

    Johnson RE, Jasinski DR . Human pharmacology and abuse potential of meptazinol. Clin Pharmacol Ther 1987; 41: 426–33.

    CAS  Article  Google Scholar 

  7. 7

    Dayer P, Collart L . Pharmacology of tramadol. Drugs 1997; 53 ( Suppl 2): 18–24.

    CAS  Article  Google Scholar 

  8. 8

    Tzschentke TM, Bruckmann W, Friderichs E . Lack of sensitization during place conditioning in rats is consistent with the low abuse potential of tramadol. Neurosci Lett 2002; 329: 25–8.

    CAS  Article  Google Scholar 

  9. 9

    Holmes B, Ward A . Meptazinol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs 1985; 30: 285–312.

    CAS  Article  Google Scholar 

  10. 10

    Ennis C, Haroun F, Lattimer N . Can the effects of meptazinol on the guinea-pig isolated ileum be explained by inhibition of acetylcholinesterase? J Pharm Pharmacol 1986; 38: 24–7.

    CAS  Article  Google Scholar 

  11. 11

    Chen Y . Studies on the synthesis, resolution and optical isomers of meptazinol. [ Dissertation]. Shanghai: Fudan Univ; 2004. p 19–28.

  12. 12

    Dewar MJS, Zoebisch EG, Healy EF, Stewart JJP . AM1: a new general purpose quantum mechanical model. J Am Chem Soc 1985; 107: 3902–9.

    CAS  Article  Google Scholar 

  13. 13

    Horn AS, Rodgers JR . The enkephalins and opiates: structure-activity relations. J Pharm Pharmacol 1977; 29: 257–65.

    CAS  Article  Google Scholar 

  14. 14

    Mackay M, Hodgkin DC . A crystallographic examination of the structure of morphine. J Chem Soc 1955; 3261.

  15. 15

    Van Den Hende JH, Nelson NR . The crystal and molecular structure of 7.alpha.-(1-(R)-hydroxy-1-methylbutyl)-6,14-endoethenotetrahydrothebaine hydrobromide (19-propylthevinol hydrobromide) J Am Chem Soc 1967; 89: 2901–5.

    CAS  Article  Google Scholar 

  16. 16

    Sasvari K, Simon K, Bognar R, Makleit S . The crystal and molecular structure of 6-deoxy-6-azido dihydroisomorphine, C17H20N4O2. Acta Cryst 1974; B30: 634–41.

    Article  Google Scholar 

  17. 17

    Fedeli W, Giacomello G, Cerrini S, Vaciago A . Crystal and molecular structure of 2-allyl-2′-hydroxy-5,9-dimethyl-6,7-benzomorphan mydrobromide monohydrate. J Chem Soc (B). 1970: 1190–5.

    CAS  Article  Google Scholar 

  18. 18

    Karle IL, Girardi RD, Fratini AV, Karle J . The crystal structures of DL-cyclazocine and L-cycla-zocine.HBr.H2O, and the absolute configuration of L-cyclazocine.HBr.H2O (2-cyclo-propylmethyl- 2′-hydroxy-5,9-dimethyl-6,7-benzomorphan). Acta Cryst 1969; B25: 146979.

    Google Scholar 

  19. 19

    Sime RL, Forehand R, Sime RJ . The crystal structure of a narcotic antagonist: naloxone hydrochloride dehydrate. Acta Cryst 1975; B31: 2326–30.

    CAS  Article  Google Scholar 

  20. 20

    Sime RJ, Dobler M, Sime RL . The crystal structure of a narcotic agonist/antagonist: nalbuphine hydrochloride dehydrate. Acta Cryst 1976; B32: 809–12.

    CAS  Article  Google Scholar 

  21. 21

    Duchesne RJ, Goodall J, Hughes IE . Pharmacological effects of meptazinol and its enantiomers on guinea-pig ileum and mouse vas deferens. J Pharm Pharmacol 1984; 36: 560–2.

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Zhui-bai Qiu.

Additional information

Project supported by the National Natural Science Foundation of China (No 30271539, 2003-2005).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, W., Hao, J., Tang, Y. et al. Structural comparisons of meptazinol with opioid analgesics. Acta Pharmacol Sin 26, 334–338 (2005). https://doi.org/10.1111/j.1745-7254.2005.00045.x

Download citation

Keywords

  • meptazinol
  • tramadol
  • opioid analgesics
  • pharmacophore

Further reading

Search