Alphaprodine

Prodine

Clinical data
ATC code	none
Legal status
Legal status	AU: S8 (Controlled) DE: Anlage I (Controlled) US: Schedule II ℞ (Prescription only)
Identifiers
IUPAC name (1,3-Dimethyl-4-phenylpiperidin-4-yl) propanoate
CAS Number	77-20-3 N 468-59-7 (beta)
PubChem (CID)	204163
ChemSpider	176845 Y
UNII	21J54X4Z4Z N
ChEMBL	CHEMBL14309 Y
Chemical and physical data
Formula	C16H23NO2
Molar mass	261.359 g/mol
3D model (Jmol)	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?)

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. 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. The compound, Ro 2-1932, is 650 percent as strong as morphine subcutaneously and 450 percent as strong as oral methadone.

There are two isomers of the trans form of prodine, alphaprodine and betaprodine. Both exhibit optical isomerism and alphaprodine and betaprodine are racemates. Alphaprodine was reported to closely related to desomorphine in steric configuration The cis form also has active isomers but not used in medicine Betaprodine is some 5x more potent than alphaprodine, 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. Betaprodine produced more euphoria and side effects than alphaprodine at all dose levels and it was found that 5 to 10 mg of betaprodine equals 25 to 40 mg of alphaprodine.

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. 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. 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.

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.

Alphaprodine was sold under several brand names, mainly Nisentil and Prisilidine. It was mainly used for pain relief in childbirth and dentistry, 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.