Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Propiram: Difference between pages

{{Short description|Opioid analgesic drug}}

{{cs1 config|name-list-style=vanc}}

| Verifiedfields = changed

| verifiedrevid = 464216831

| IUPAC_name = ''N''-(1-Methyl-2-piperidin-1-ylethyl)-''N''-pyridin-2-ylpropanamide

| image = Propiram2DCSD.svg

| legal_AU = S8

| legal_BR = A2

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-03 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_CA = Schedule I

| legal_DE = Anlage II

| routes_of_administration = [[Oral administration|By mouth]], injected

| excretion =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 15686-91-6

'''Propiram''' ('''Algeril''', '''Dirame''', '''Bay 4503''')<ref>US3163654A Pyridine derivatives and their preparation (n-tertiary aminoalkyl-n-acyl)-amino pyridines</ref> is a partial [[μ-opioid receptor]] agonist and weak μ antagonist [[analgesic]] from the ampromide family of drugs related to other drugs such as [[phenampromide]] and [[diampromide]]. It was invented in 1963 in the United Kingdom by Bayer<ref>{{US Patent|3163654}}</ref> but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached [[Phase III clinical trial]]s in the United States and Canada.<ref>{{cite book | title = Drug Facts & Comparisons | edition = 56th | date = 2002}}</ref>

==Pharmacology==

Propiram exhibits weak opioid antagonist activity on the μ receptor—quite a bit weaker than its agonist effects—and the effect on [[kappa-opioid receptor|κ-]] and [[delta-opioid receptor|δ-opioid]], [[sigma receptor|σ-receptors]], or the [[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&nbsp;mg of propiram is equivalent to about 60&nbsp;mg of codeine or 50&nbsp;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&nbsp;mg and a duration of action of 3 to 6 hours.<ref>{{cite journal | vauthors = Wilson RS, Landers JH | title = Use of a new oral analgesic, propiram fumarate, in treating postoperative ocular pain | journal = Annals of Ophthalmology | volume = 14 | issue = 12 | pages = 1172–4 | date = December 1982 | pmid = 7165237 }}</ref> It is more potent and effective than codeine,<ref>{{cite journal | vauthors = Desjardins PJ, Cooper SA, Gallegos TL, Allwein JB, Reynolds DC, Kruger GO, Beaver WT | title = The relative analgesic efficacy of propiram fumarate, codeine, aspirin, and placebo in post-impaction dental pain | journal = Journal of Clinical Pharmacology | volume = 24 | issue = 1 | pages = 35–42 | date = January 1984 | pmid = 6368614 | doi = 10.1002/j.1552-4604.1984.tb01811.x | s2cid = 11070740 }}</ref> and longer-lasting and with a faster onset of action compared to pethidine.<ref>{{cite journal | vauthors = Korduba CA, Veals J, Radwanski E, Symchowicz S, Chung M | title = Bioavailability of orally administered propiram fumarate in humans | journal = Journal of Pharmaceutical Sciences | volume = 70 | issue = 5 | pages = 521–3 | date = May 1981 | pmid = 7241356 | doi = 10.1002/jps.2600700515 }}</ref> Side effects include [[sedation]], [[dizziness]], [[nausea]] and [[vomiting]].<ref>{{cite journal | vauthors = Goa KL, Brogden RN | title = Propiram. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use as an analgesic | journal = Drugs | volume = 46 | issue = 3 | pages = 428–445 | date = September 1993 | pmid = 7693433 | doi = 10.2165/00003495-199346030-00008 | s2cid = 195691876 }}</ref> 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.<ref>{{cite journal | vauthors = Hiltmann R, Hoffmeister F, Niemers E, Schlichting U, Wollweber H | title = [2-Acylaminopyridine derivatives with morphine agonistic and morphine antagonistic effects] | journal = Arzneimittel-Forschung | volume = 24 | issue = 4 | pages = 584–600 | date = April 1974 | pmid = 4406861 }}</ref> 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 <ref>Wollweber H. Stereochemische Untersuchungen über Arzneimittel. ''European Journal of Medicinal Chemistry'' 1982; 17: 125–133.</ref> 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.

[[Image:Propiram-derivatives_structure.png|280px|thumb|left|3,3-Dimethylpropiram, CAS# 24639-20-1, and 4-Phenylpropiram, CAS# 54152-81-7]]{{clear-left}}

==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 [[Pharmaceutical formulation|formulated]] as the [[fumarate]] [[salt (chemistry)|salt]].

== References ==

{{Reflist|2}}

{{Opioidergics}}

[[Category:Opioids]]

[[Category:2-Pyridyl compounds]]

[[Category:1-Piperidinyl compounds]]

[[Category:Propionamides]]