Prodine

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Prodine
Skeletal formula of prodine
Ball-and-stick model of the prodine molecule
Clinical data
ATC code none
Legal status
Legal status
Identifiers
CAS Number 77-20-3 N
468-59-7 (beta)
PubChem (CID) 204163
ChemSpider 176845 YesY
UNII 21J54X4Z4Z N
ChEMBL CHEMBL14309 YesY
Chemical and physical data
Formula C16H23NO2
Molar mass 261.359 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Prodine (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.

Several 1-alkyl-4-phenyl-4-acyloxypiperidines have been prepared and found to possess significant analgesic action.[1] Those compounds with the 4-propionoxy substituent appear to be the most potent analgesics. Ziering and Lee found that embellishing this structure via the incorporation of a 3-methyl group into the piperidine nucleus greatly enhanced the pharmacological activity.[2] The compound, Ro 2-1932, is 650 per cent as strong as morphine subcutaneously and 450 per cent as strong as oral methadone.[3]

There are two isomers of the trans form of prodine, alphaprodine and betaprodine. Both exhibit optical isomerism and alphaprodine and betaprodine are racemates.[4] Alphaprodine was reported to closely related to desomorphine in steric configuration[5] The cis form also has active isomers but not used in medicine [6][7] Betaprodine is some 5x more potent than alphaprodine,[8] but is metabolised more rapidly, and only alphaprodine was developed for medicinal use. It has similar activity to pethidine, but with a faster onset of action and shorter duration.[9] Betaprodine produced more euphoria and side effects than alphaprodine at all dose levels[10] and it was found that 5 to 10 mg of betaprodine equals 25 to 40 mg of alphaprodine.[11]

Tests in rats showed alphaprodine to be 97 per cent the strength of morphine via the subcutaneous route and 140 per cent the strength of methadone orally.[12] Betaprodine was 550 per cent as strong as morphine SC, and the laevorotary cis isomer was 350 per cent as strong, and the dextrorotary cis isomer was 790 per cent was strong.[13] Betaprodine by mouth was 420 per cent as strong as methadone, and the cis form was 390 per cent for the laevo and 505 per cent for the dextro isomers.[14]

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

Prodine isomers.png

Alphaprodine was sold under several brand names, mainly Nisentil and Prisilidine. It was mainly used for pain relief in childbirth[15] and dentistry,[16] as well as for minor surgical procedures. Alphaprodine has a duration of action of 1 to 2 hours and 40 to 60 mg is equal to 10 mg of morphine via the subcutaneous route.

Prodine has similar effects to other opioids, and produces analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. Respiratory depression can be a problem with alphaprodine even at normal therapeutic doses.[17] Unlike pethidine, prodine does not produce toxic metabolites and is therefore more suitable for high-dose therapy.[medical citation needed]

See also[edit]

References[edit]

  1. ^ Ziering, A.; Berger, L. E. O.; Heineman, S. D.; Lee, J. (1947). "Piperidine Derivatives. Part III. 4-Arylpiperidines". The Journal of Organic Chemistry. 12 (6): 894. doi:10.1021/jo01170a022. PMID 18919742. 
  2. ^ Ziering, A.; Lee, J. (1947). "Piperidine Derivatives. V. 1,3-Dialkyl-4-Aryl-4-Acyloxypiperidines". The Journal of Organic Chemistry. 12 (6): 911–4. doi:10.1021/jo01170a024. PMID 18919744. 
  3. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  4. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  5. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  6. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  7. ^ 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. 
  8. ^ John Bedford Stenlake. Foundations of Molecular Pharmacology. ISBN 0-485-11171-3. 
  9. ^ 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. 
  10. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  11. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-312
  12. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  13. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  14. ^ Reynolds & Randall, Morphine & Allied Drugs (1957) pp 310-311
  15. ^ Burnett RG, White CA (1966). "Alphaprodine for continuous intravenous obstetric analgesia". Obstetrics & Gynecology. 27 (4): 472–477. doi:10.1097/00006250-196604000-00003. 
  16. ^ 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. 
  17. ^ 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. 
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