Alazocine

Source: Wikipedia, the free encyclopedia.
Not to be confused with
N-Allylnormorphine
.
Alazocine
Clinical data
Other namesSKF-10047; WIN-19631; N-Allylnormetazocine; NANM; NAN; ANMC; 2'-Hydroxy-5,9-dimethyl-2-allyl-6,7-benzomorphan
ATC code
  • None
Identifiers
  • (±)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propen-1-yl)-2,6-methano-3-benzazocin-8-ol
JSmol)
  • CC1C2CC3=C(C1(CCN2CC=C)C)C=C(C=C3)O
  • InChI=1S/C17H23NO/c1-4-8-18-9-7-17(3)12(2)16(18)10-13-5-6-14(19)11-15(13)17/h4-6,11-12,16,19H,1,7-10H2,2-3H3 checkY
  • Key:LGQCVMYAEFTEFN-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Alazocine (developmental code name SKF-10047), also known more commonly as N-allylnormetazocine (NANM), is a

label the σ1 receptor, and led to the discovery and characterization of the receptor.[4][5]

Pharmacology

Pharmacodynamics

Alazocine shows

HEK293 cells)[8] and as an antagonist of the μ-opioid receptor (Ki = 1.15 nM for (±)-alazocine against the mouse receptor transfected in HEK293 cells).[9] It is also an agonist of the δ-opioid receptor with far lower potency (Ki = not reported, IC50 = 184 nM, and Imax = 68% for (±)-alazocine against the mouse receptor transfected in HEK293 cells).[10]

Conversely, the (+)-

uncompetitive NMDA receptor antagonist as well at higher concentrations.[11] As such, (+)-alazocine is only modestly selective as a ligand of the σ1 receptor.[11]

Both enantiomers of alazocine have very low affinity for the sigma

radioligand binding assays.[11][5]

Taken together, (–)-alazocine is a selective partial agonist of the κ-opioid receptor, antagonist of the μ-opioid receptor, and to a far lesser extent agonist of the δ-opioid receptor[8][9][10] with very low affinity for the sigma receptors, while (+)-alazocine is a selective agonist of the sigma σ1 receptor and to a lesser (~10-fold) extent antagonist of the NMDA receptor with low affinity for the opioid and sigma σ2 receptors.[6][7][11][5]

History

Alazocine was one of the early members of the benzomorphan family of opioid analgesics to be investigated.[1] It was first described in the scientific literature in 1961.[12] Its development resulted from nalorphine (N-allylnormorphine), a potent analgesic and opioid antagonist with similar pharmacology which had been introduced in the mid-1950s.[1] Alazocine was found to produce strong psychotomimetic effects in humans, and it was not further developed for clinical use.[13][1] Subsequently, other benzomorphans, such as pentazocine (an N-dimethylallylbenzomorphan), cyclazocine (an N-cyclopropylmethylbenzomorphan), and phenazocine (an N-phenylethylbenzomorphan), were developed, and some have been marketed for use as analgesics.[1]

The sigma σ1 receptor was named in 1976 and (+)-alazocine was described as its prototypical ligand.

(+)-3-PPP, which show similar affinity for both subtypes).[7]

References

  1. ^
    ISBN 978-1-4899-0585-7
    .
  2. ^
    ISSN 0065-2393
    .
  3. PMID 6783955
    .
  4. ^
    PMID 21428827
    .
  5. ^
    S2CID 72726251
    .
  6. ^
    PMID 2986989
    .
  7. ^
    S2CID 24546226
    .
  8. ^
    PMID 16433932
    .
  9. ^
    PMID 12513698
    .
  10. ^
    PMID 12437765
    .
  11. ^
    S2CID 22762264
    .
  12. S2CID 4212447
    .
  13. ^
    ISBN 978-3-642-46660-1
    .
  14. ^
    ISBN 978-3-540-74806-9
    .
  15. PMID 945347
    .
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