Prodine

Opioid analgesic

Pharmaceutical compound

Prodine

Skeletal formula of prodine

Ball-and-stick model of the alphaprodine molecule

Clinical data
ATC code|

* none

Legal status
Legal status|

* AU: S8 (Controlled drug)
* BR: Class A1 (Narcotic drugs)[1]
* DE: Anlage I (Authorized scientific use only)
* US: Schedule I
* In general: ℞ (Prescription only)

Identifiers

IUPAC name

* (1,3-Dimethyl-4-phenylpiperidin-4-yl) propanoate

CAS Number|

* 77-20-3 Y (alpha)
* 468-59-7 Y (beta)

PubChem CID|

* 204163

ChemSpider|

* 176845 Y

UNII|

* 001O2254AC
* 21J54X4Z4Z Y

KEGG|

* D12678 Y
* D12679 Y

ChEMBL|

* ChEMBL14309 Y

CompTox Dashboard (EPA)|

* DTXSID70859103

Chemical and physical data
Formula| C16H23NO2
Molar mass| 261.365 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* O=C(CC)O[C@]1(CCN(C[C@H]1C)C)C2=CC=CC=C2

InChI

* InChI=1S/C16H23NO2/c1-4-15(18)19-16(14-8-6-5-7-9-14)10-11-17(3)12-13(16)2/h5-9,13H,4,10-12H2,1-3H3/t13-,16+/m1/s1 Y

* Key:UVAZQQHAVMNMHE-CJNGLKHVSA-N Y

NY (what is this?)  (verify)

Prodine[2] (trade names Prisilidine and Nisentil) is an opioid analgesic that is an analog of pethidine (meperidine). It was developed in Germany in the late 1940s.

There are two isomers of the trans form of prodine, alphaprodine and betaprodine. Both exhibit optical isomerism and alphaprodine and betaprodine are racemates.[3] Alphaprodine is closely related to desomorphine in steric configuration.[3] The cis form also has active isomers but none are used in medicine.[3][4] Betaprodine is around five times more potent than alphaprodine[5] but is metabolized more rapidly, and only alphaprodine was developed for medicinal use. It has similar activity to pethidine, but with a more rapid onset and shorter duration of effects.[6] Betaprodine produces more euphoria and side effects than alphaprodine at all dose levels, and it was found that 5 to 10 mg of betaprodine is equivalent to 25 to 40 mg of alphaprodine.[3]

Testing in rats showed alphaprodine to be 97% the strength of morphine via the subcutaneous route and 140% the strength of oral methadone.[3] Betaprodine was 550% stronger than morphine SC, the laevorotatory cis isomer was 350% stronger, and the dextrorotatory cis isomer was 790% stronger.[3] Betaprodine taken orally was 420% stronger than oral methadone, the cis form was 390% stronger for the laevorotatory and 505% stronger for the dextrorotatory isomers.[3]

Alphaprodine was sold under several brand names, mainly Nisentil and Prisilidine. It was most commonly used for pain relief during childbirth[7] and dentistry,[8] as well as for some minor surgical procedures. Alphaprodine has a duration of action of 1 to 2 hours, and 40 to 60 mg is equivalent to 10 mg of subcutaneous morphine.

Prodine has broadly similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include excessive itching, nausea, vomiting and potentially serious respiratory depression which can lead to life-threatening respiratory arrest. Respiratory depression can be a problem with alphaprodine even at normal therapeutic doses.[9] Unlike pethidine, prodine does not produce toxic metabolites and is therefore more suitable for high-dose therapy.[medical citation needed]

## Regulation

[edit]

Alphaprodine has a DEA ACSCN of 9010 and 2013 manufacturing quota of 3 grams; betaprodine has an ACSCN of 9611 and a 2 grams quota.

## See also

[edit]

* Proheptazine
* Trimeperidine

## References

[edit]

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 2023-08-16.
2. ^ US Patent 2498433 '1,3 dimethyl-4-propionoxy-4-phenyl-piperidine and acid addition salts thereof'
3. ^ a b c d e f g Reynolds AK, Randall LO (1957). Morphine & Allied Drugs. University of Toronto Press. pp. 310–312\. OCLC 1628783.
4. ^ Beckett AH, Walker J (1955). "The configuration of alphaprodine and betaprodine". Journal of Pharmacy and Pharmacology. 7 (1): 1039–1045\. doi:10.1111/j.2042-7158.1955.tb12115.x. PMID 13278850. S2CID 46012276.
5. ^ Stenlake JB (1979). Foundations of Molecular Pharmacology. ISBN 978-0-485-11171-2.
6. ^ Fung DL, Asling JH, Eisele JH, Martucci R (1980). "A comparison of alphaprodine and meperidine pharmacokinetics". Journal of Clinical Pharmacology. 20 (1): 37–41\. doi:10.1002/j.1552-4604.1980.tb01664.x. PMID 7358866. S2CID 35046059.
7. ^ Burnett RG, White CA (1966). "Alphaprodine for continuous intravenous obstetric analgesia". Obstetrics & Gynecology. 27 (4): 472–477\. doi:10.1097/00006250-196604000-00003. PMID 5907367.
8. ^ Carter WJ, Bogert JA (1966). "An effective pre-medication procedure for dental patients". Journal of the Missouri Dental Association. 46 (6): 8–9\. PMID 5221807.
9. ^ Fuller JD, Crombleholme WR (1987). "Respiratory arrest and prolonged respiratory depression after one low, subcutaneous dose of alphaprodine for obstetric analgesia. A case report". Journal of Reproductive Medicine. 32 (2): 149–151\. PMID 3560080.

* v
* t
* e

Opioid receptor modulators

μ-opioid
(MOR)|

| Agonists
(abridged;
full list)|

* 3-HO-PCP
* 7-Acetoxymitragynine
* 7-Hydroxymitragynine
* ψ-Akuammigine
* α-Chlornaltrexamine
* α-Narcotine
* Acetyldihydrocodeine
* Acetylfentanyl
* Acrylfentanyl
* Adrenorphin (metorphamide)
* AH-7921
* Akuammicine
* Akuammidine
* Alfentanil
* Anileridine
* Apparicine
* β-Endorphin
* BAM-12P
* BAM-18P
* BAM-22P
* Benzhydrocodone
* Benzylmorphine
* Bezitramide
* Biphalin
* BU08070
* Buprenorphine
* Butorphan
* Butorphanol
* Butyrfentanyl
* BW373U86
* Carfentanil
* Casokefamide
* Cebranopadol
* Chloroxymorphamine
* Codeine
* DADLE
* DAMGO (DAGO)
* Dermorphin
* Desmetramadol (desmethyltramadol)
* Desomorphine
* Deumitragynine
* Dextromoramide
* Dextropropoxyphene (propoxyphene)
* Dezocine
* Dimenoxadol
* Dimethylaminopivalophenone
* Eluxadoline
* Diamorphine (heroin)
* Dihydrocodeine
* Dihydroetorphine
* Dihydromorphine
* Dinalbuphine sebacate
* Diphenoxylate
* Dipipanone
* Dynorphin A
* Embutramide
* Endomorphin-1
* Endomorphin-2
* Eseroline
* Ethylmorphine
* Etorphine
* Fentanyl
* Fluorophen
* Frakefamide
* Furanylfentanyl
* Hemorphin-4
* Herkinorin
* Hodgkinsine
* Hydrocodone
* Hydromorphinol
* Hydromorphone
* IBNtxA
* Ketamine
* Ketobemidone
* Kratom
* Laudanosine
* Lefetamine
* Leu-enkephalin
* Levacetylmethadol
* Levomethorphan
* Levorphanol
* Lexanopadol
* Loperamide
* Loxicodegol
* LS-115509
* Matrine
* Meptazinol
* Met-enkephalin (metenkefalin)
* Methadone
* Metkefamide
* Metopon
* Mitragynine
* Mitragynine pseudoindoxyl
* Morphiceptin
* Morphine
* Nalbuphine
* Naloxone benzoylhydrazone (NalBzOH)
* Nalmexone
* Naltalimide
* Neopine
* NFEPP
* Nicocodeine
* Nicodicodine
* Nicomorphine
* Norketamine
* Nufenoxole
* Octreotide
* Oliceridine
* Oxycodegol
* Oxymorphone-3-methoxynaltrexonazine (OM-3-MNZ)
* Oripavine
* Oxycodone
* Oxymorphazone
* Oxymorphonazine
* Oxymorphone
* Oxymorphone phenylhydrazone
* OxyPNPH
* Papaver somniferum (opium)
* Pentazocine
* Pericine
* Pethidine (meperidine)
* Phenazocine
* Phencyclidine
* Piminodine
* Piritramide
* PL-017
* Prodine
* Propiram
* PZM21
* Racemethorphan
* Racemorphan
* Remifentanil
* Salsolinol
* SC-17599
* Sinomenine
* Sufentanil
* Tapentadol
* Tetrahydropapaveroline
* TH-030418
* Thebaine
* Thienorphine
* Tianeptine
* Tilidine
* Tramadol
* Trimebutine
* TRIMU 5
* TRV734
* Tubotaiwine
* U-47700
* Valorphin
* Viminol
* Xorphanol

|

Antagonists|

* (3S,4S)-Picenadol
* 2-(S)-N,N-(R)-Viminol
* 3CS-nalmefene
* 4-Caffeoyl-1,5-quinide
* 4′-Hydroxyflavanone
* 4',7-Dihydroxyflavone
* 6β-Naltrexol
* 6β-Naltrexol-d4
* 18-MC
* α-Gliadin
* β-Chlornaltrexamine
* β-Funaltrexamine
* Akuammine
* Alvimopan
* AM-251
* Apigenin
* AT-076
* Axelopran
* Bevenopran
* Catechin
* Catechin gallate
* Clocinnamox
* CTAP
* CTOP
* Cyclofoxy
* Cyprodime
* Diacetylnalorphine
* Diprenorphine
* ECG
* EGC
* Epicatechin
* Eptazocine
* Gemazocine
* Ginsenoside R
* Hyperoside
* Ibogaine
* JDTic
* Levallorphan
* Lobeline
* LY-255582
* LY-2196044
* Methocinnamox
* Methylnaltrexone
* Methylsamidorphan chloride
* Naldemedine
* Nalmefene
* Nalodeine (N-allylnorcodeine)
* Nalorphine
* Nalorphine dinicotinate
* Naloxazone
* Naloxegol
* Naloxol
* Naloxonazine
* Naloxone
* Naltrexazone
* Naltrexonazine
* Naltrexone
* Naltrindole
* Naringenin
* Noribogaine
* Oxilorphan
* Pawhuskin A
* Rimonabant
* Quadazocine
* Samidorphan
* Taxifolin

δ-opioid
(DOR)|

| Agonists|

* 3CS-nalmefene
* 6'-GNTI
* 7-SIOM
* ADL-5747 (PF-04856881)
* ADL-5859
* Alazocine (SKF-10047)
* Amoxapine
* AR-M100390 (ARM390)
* AZD2327
* β-Endorphin
* BAM-18P
* Biphalin
* BU-48
* Butorphan
* Butorphanol
* BW373U86
* Casokefamide
* Cebranopadol
* Codeine
* Cyclazocine
* DADLE
* Deltorphin A
* Deltorphin I
* Deltorphin II
* Desmethylclozapine
* Desmetramadol (desmethyltramadol)
* Dezocine
* Diamorphine (heroin)
* Dihydroetorphine
* Dihydromorphine
* DPDPE
* DPI-221
* DPI-3290
* DSLET
* Ethylketazocine
* Etorphine
* Fentanyl
* FIT
* Fluorophen
* Hemorphin-4
* Hydrocodone
* Hydromorphone
* Ibogaine
* Isomethadone
* JNJ-20788560
* KNT-127
* Kratom
* Laudanosine
* Leu-enkephalin
* Levomethorphan
* Levorphanol
* Lexanopadol
* Lofentanil
* Met-enkephalin (metenkefalin)
* Metazocine
* Metkefamide
* Mitragynine
* Mitragynine pseudoindoxyl
* Morphine
* N-Phenethyl-14-ethoxymetopon
* Norbuprenorphine
* NalBzOH
* Oripavine
* Oxycodone
* Oxymorphone
* Pethidine (meperidine)
* Proglumide
* Racemethorphan
* Racemorphan
* RWJ-394674
* Samidorphan
* SB-235863
* SNC-80
* SNC-162
* TAN-67 (SB-205,607)
* TH-030418
* Thebaine
* Thiobromadol (C-8813)
* Tonazocine
* Tramadol
* TRV250
* Xorphanol
* Zenazocine

|

Antagonists|

* 4',7-Dihydroxyflavone
* 5'-NTII
* 6β-Naltrexol
* 6β-Naltrexol-d4
* α-Santolol
* β-Chlornaltrexamine
* Apigenin
* AT-076
* Axelopran
* Bevenopran
* BNTX
* Catechin
* Catechin gallate
* Clocinnamox
* Diacetylnalorphine
* Diprenorphine
* ECG
* EGC
* Eluxadoline
* Epicatechin
* ICI-154129
* ICI-174864
* LY-255582
* LY-2196044
* Methylnaltrexone
* Methylnaltrindole
* N-Benzylnaltrindole
* Nalmefene
* Nalorphine
* Naltrexone
* Naltriben
* Naltrindole
* Naloxone
* Naringenin
* Noribogaine
* Pawhuskin A
* Quadazocine
* SDM25N
* SoRI-9409
* Taxifolin
* Thienorphine

κ-opioid
(KOR)|

| Agonists|

* 3CS-nalmefene
* 6'-GNTI
* 8-CAC
* 18-MC
* 14-Methoxymetopon
* β-Chlornaltrexamine
* β-Funaltrexamine
* Adrenorphin (metorphamide)
* Akuammicine
* Alazocine (SKF-10047)
* Allomatrine
* Apadoline
* Asimadoline
* BAM-12P
* BAM-18P
* BAM-22P
* Big dynorphin
* Bremazocine
* BRL-52537
* Butorphan
* Butorphanol
* BW373U86
* Cebranopadol
* Ciprefadol
* CR665
* Cyclazocine
* Cyclorphan
* Cyprenorphine
* Desmetramadol (desmethyltramadol)
* Diamorphine (heroin)
* Diacetylnalorphine
* Difelikefalin
* Dihydroetorphine
* Dihydromorphine
* Dinalbuphine sebacate
* Diprenorphine
* Dynorphin A
* Dynorphin B (rimorphin)
* Eluxadoline
* Enadoline
* Eptazocine
* Erinacine E
* Ethylketazocine
* Etorphine
* Fedotozine
* Fentanyl
* Gemazocine
* GR-89696
* GR-103545
* Hemorphin-4
* Herkinorin
* HS665
* Hydromorphone
* HZ-2
* Ibogaine
* ICI-199,441
* ICI-204,448
* Ketamine
* Ketazocine
* Laudanosine
* Leumorphin (dynorphin B-29)
* Levallorphan
* Levomethorphan
* Levorphanol
* Lexanopadol
* Lofentanil
* LPK-26
* Lufuradom
* Matrine
* MB-1C-OH
* Menthol
* Metazocine
* Metkefamide
* Mianserin
* Mirtazapine
* Morphine
* Moxazocine
* MR-2034
* N-MPPP
* Nalbuphine
* NalBzOH
* Nalfurafine
* Nalmefene
* Nalodeine (N-allylnorcodeine)
* Nalorphine
* Naltriben
* Niravoline
* Norbuprenorphine
* Norbuprenorphine-3-glucuronide
* Noribogaine
* Norketamine
* Oripavine
* Oxa-noribogaine
* Oxilorphan
* Oxycodone
* Pentazocine
* Pethidine (meperidine)
* Phenazocine
* Proxorphan
* Racemethorphan
* Racemorphan
* RB-64
* Salvinorin A (salvia)
* Salvinorin B ethoxymethyl ether
* Salvinorin B methoxymethyl ether
* Samidorphan
* Spiradoline (U-62066)
* TH-030418
* Thienorphine
* Tifluadom
* Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline)
* U-50488
* U-54494A
* U-69593
* Xorphanol

|

Antagonists|

* 4′-Hydroxyflavanone
* 4',7-Dihydroxyflavone
* 5'-GNTI
* 6'-GNTI
* 6β-Naltrexol
* 6β-Naltrexol-d4
* β-Chlornaltrexamine
* Buprenorphine/samidorphan
* Amentoflavone
* ANTI
* Apigenin
* Arodyne
* AT-076
* Aticaprant
* Axelopran
* AZ-MTAB
* Binaltorphimine
* BU09059
* Buprenorphine
* Catechin
* Catechin gallate
* CERC-501 (LY-2456302)
* Clocinnamox
* CVL-354
* Cyclofoxy
* Dezocine
* DIPPA
* EGC
* ECG
* Epicatechin
* Hyperoside
* JDTic
* LY-255582
* LY-2196044
* LY-2444296
* LY-2459989
* LY-2795050
* MeJDTic
* Methylnaltrexone
* ML190
* ML350
* MR-2266
* N-Fluoropropyl-JDTic
* Naloxone
* Naltrexone
* Naltrindole
* Naringenin
* Navacaprant
* Norbinaltorphimine
* Noribogaine
* Pawhuskin A
* PF-4455242
* RB-64
* Quadazocine
* Taxifolin
* UPHIT
* Zyklophin

Nociceptin
(NOP)|

| Agonists|

* (Arg14,Lys15)Nociceptin
* ((pF)Phe4)Nociceptin(1-13)NH2
* (Phe1Ψ(CH2-NH)Gly2)Nociceptin(1-13)NH2
* Ac-RYYRWK-NH2
* Ac-RYYRIK-NH2
* BU08070
* Buprenorphine
* Cebranopadol
* Dihydroetorphine
* Etorphine
* JNJ-19385899
* Levomethorphan
* Levorphanol
* Lexanopadol
* MCOPPB
* MT-7716
* NNC 63-0532
* Nociceptin (orphanin FQ)
* Nociceptin (1-11)
* Nociceptin (1-13)NH2
* Norbuprenorphine
* Racemethorphan
* Racemorphan
* Ro64-6198
* Ro65-6570
* SCH-221510
* SCH-486757
* SR-8993
* SR-16435
* Sunobinop (S-117957)
* TH-030418

|

Antagonists|

* (Nphe1)Nociceptin(1-13)NH2
* AT-076
* BAN-ORL-24
* BTRX-246040 (LY-2940094)
* J-113397
* JTC-801
* NalBzOH
* Nociceptin (1-7)
* Nocistatin
* SB-612111
* SR-16430
* Thienorphine
* Trap-101
* UFP-101

Others|

* Enkephalinase inhibitors: Amastatin
* BL-2401
* Candoxatril
* D-Phenylalanine
* Dexecadotril (retorphan)
* Ecadotril (sinorphan)
* Kelatorphan
* Racecadotril (acetorphan)
* RB-101
* RB-120
* RB-3007
* Opiorphan
* Selank
* Semax
* Spinorphin
* Thiorphan
* Tynorphin
* Ubenimex (bestatin)

* Propeptides: β-Lipotropin (proendorphin)
* Prodynorphin
* Proenkephalin
* Pronociceptin
* Proopiomelanocortin (POMC)

* Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)

*[AU]: Australia
*[BR]: Brazil
*[DE]: Germany
*[US]: United States
*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
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