Propiram

Source: Wikipedia, the free encyclopedia.
Propiram
Clinical data
Routes of
administration
By mouth, injected
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Bioavailability97%
Elimination half-life5.2 hours
Identifiers
  • N-(1-Methyl-2-piperidin-1-ylethyl)-N-pyridin-2-ylpropanamide
JSmol)
  • O=C(N(c1ncccc1)C(CN2CCCCC2)C)CC
  • InChI=1S/C16H25N3O/c1-3-16(20)19(15-9-5-6-10-17-15)14(2)13-18-11-7-4-8-12-18/h5-6,9-10,14H,3-4,7-8,11-13H2,1-2H3 checkY
  • Key:ZBAFFZBKCMWUHM-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Propiram (Algeril, Dirame, Bay 4503)

Phase III clinical trials in the United States and Canada.[4]

Pharmacology

Propiram exhibits weak opioid antagonist activity on the μ receptor—quite a bit weaker than its agonist effects—and the effect on

NMDA system are not well understood. Other drugs of the partial μ-opioid agonist/antagonist type include meptazinol, buprenorphine, butorphanol, phenazocine, nalbuphine, pentazocine, dezocine
and its relatives.

With about 10% of the analgesic potency of morphine, 50 mg of propiram is equivalent to about 60 mg of codeine or 50 mg of pentazocine. In many patients, propiram is an effective analgesic comparable to other drugs such as these as well as pethidine, with a normal dose of around 50–100 mg and a duration of action of 3 to 6 hours.[5] It is more potent and effective than codeine,[6] and longer-lasting and with a faster onset of action compared to pethidine.[7] Side effects include sedation, dizziness, nausea and vomiting.[8] Propiram has been available in oral, rectal, and injectable formulations, with bioavailability above 97% after oral administration.

Derivatives

Many related compounds are known, although only propiram was ever commercialized.[9] The addition of a 4-phenyl group on the piperidine increases potency by a factor of 133x compared to the parent compound. Addition of a 3,3-dimethyl moiety to the piperidine ring increases potency by 45x compared to the title compound [10] and 3D overlay using CHARMM shows that this class overlays the fentanyl scaffold in the positioning of aryl groups, basic nitrogen and amide moieties perfectly.

3,3-Dimethylpropiram, CAS# 24639-20-1, and 4-Phenylpropiram, CAS# 54152-81-7

Regulation

Propiram is currently a Schedule I/Narcotic controlled substance in the United States with an ACSCN of 9649 and a zero annual aggregate manufacturing quota as of 2014. It has been almost exclusively

fumarate salt
.

References

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-03.
  2. ^ US3163654A Pyridine derivatives and their preparation (n-tertiary aminoalkyl-n-acyl)-amino pyridines
  3. ^ U.S. patent 3,163,654
  4. ^ Drug Facts & Comparisons (56th ed.). 2002.
  5. PMID 7165237
    .
  6. .
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  9. .
  10. ^ Wollweber H. Stereochemische Untersuchungen über Arzneimittel. European Journal of Medicinal Chemistry 1982; 17: 125–133.