1 - -dihydrocodeine

ANTTBIOTTCS - BETA-LACTAMS - BETA-LACTAMASEINHIBITORS] (Vol 3) Dihydrocodeine [125-28-0]... 

Dihydrocodeine [125-28-0] (33), introduced in Germany before 1930, and dihydrocodeinone enol acetate [466-90-0] (34) both have clinical activity and addiction potential comparable to codeine. 

Dihydrocodeine [125-28-0] M 301.4, m 112-113°, b 248/14mm . Crystd from aqueous methanol. 

Numerous derivati es of morphine have been devised for use in medicine including acyl derivatives, of which diacetylmorphine (C], Hj,03N, Ac2, m.p. 173°, [a]J°° — 166° (MeOH) B. HCl. 2H2O, m.p. 231-2°) is the best known, alkyl and other ethers such as the ethyl-and benzyl-morphines, dihydro- and dihydroketo-compounds such as dihydromorphine, dihydrocodeine, dihydromorphinone, dihydrocodeinone and hydroxydihydrocodcinone, and the deoxy-compounds, e.g., dihydro-deoxymorphine and methyldihydrodeoxymorphine. 

Dihydrocinchonicine, 452 Dihydrocinchonidine, 429 Dihydrocinchonine, 428 Dihydrocinchotoxine, 452 Dihydrocodeine, 260 Dihydrocodeinone, 245, 260, 270 Dihydroeodeinone oxime, reactions, 244 Dihydromeiacodeinone, 249 Dihydrocryptopine and isodihydrocryptopine, 296 Dihydrocupreicine, 452 Dihydrocupreidine, 431 Dihydrocupreine, 431 Dihydrodeoxymorphines, 254, 260-2 Dihydroecgonidine, 99 Dihydro- -erythroidines, 387... 

Catalytic reduction of codeine (2) affords the analgesic dihydrocodeine (7) Oxidation of the alcohol at 6 by means of the Oppenauer reaction gives hydrocodone (9)an agent once used extensively as an antitussive. It is of note that treatment of codeine under strongly acidic conditions similarly affords hydrocodone by a very unusual rearrangement of an allyl alcohol to the corresponding enol, followed by ketonization. 

Figure 11.12 GC analysis of (a) urine sample spiked with opiates 3 p.g/ml) and (b) blank urine sample. Peak identification is as follows 1, dihydrocodeine 2, codeine 3, ethylmor-phine 4, moipliine 5, heroin. Reprinted from Journal of Chromatography, A 771, T. Hyotylainen et al., Determination of morphine and its analogues in urine by on-line coupled reversed-phase liquied cliromatography-gas clrromatography with on-line derivatization, pp. 360-365, copyright 1997, with permission from Elsevier Science.

See also glycerol monostearate dihydrocodeine, 183 dihydroxybutane. See butylene glycol dihydroxyethane. See ethylene glycol dihydroxypropane. See propylene glycol... 

Irreversible reaction of [18] iodine with acetylsalicylic acid, aethaverine, amidopyrine, ascorbic acid, benzo-caine, quinine, dihydrocodeine, fluorescein, glycine, hydrocortisone acetate, isoni-azid, metamizole, papaverine, paracetamol, phenacetin, phenol-phthalein, piperazine, resorcinol, salicylic acid, salicylamide, sulfaguanidine, thymol, triethanolamine, tris buffer detection by reaction chromatography... 

Mignat C, Wille U, Ziegler A. (1995). Affinity profiles of morphine, codeine, dihydrocodeine, and their glucuronides at opioid receptor subtypes. Life Sci. 56(10) 793-99. 

Dienestrol, 102, 103 Diethyl carbamazine, 278 Diethylstilbestrol, 101 Diethylthiambutene, 106 Dihexyrevine, 36 Dihydralazine, 353 Dihydrocodeine, 288 Dihydropteroic acid, in bacterial metabolism, 121 Diketene, addition to imines,... 

Catalytic reduction of codeine gives dihydrocodeine and Oppenauer oxidation (a ketone such as acetone and an aluminum alkoxide, the ketone being reduced to an alcohol) gives hydrocodone. Hydrocodone can also be prepared directly from codeine with a metal catalyst, which isomerizes the allylic alcohol to a ketone. Codeine is prepared by methylation of morphine, which is isolated from the opium poppy. Hydrocodone is more potent than codeine. Acetaminophen is a mild analgesic and is discussed in Section 8. 

Hydrocodone Hydrocodone, 4,5-epoxy-3-methoxy-Af-methyl-6-oxomorphinane (3.1.27), is a compound that is chemically related to morphine and codeine. Hydrocodone is synthesized by the isomerization of codeine (3.1.20) using a palladium or platinum catalyst [18]. This drug has also been suggested to be synthesized by the hydration of codeinone [19] and by oxidation of dihydrocodeine [20]. 

The above mentioned reactions are widely used in alkaloid modification. A good example of alkaloid modifications for clinical curation purposes are opioides. Morphine and codeine are natural products of Papaver somniferum. However, the codeine is naturally produced in small amounts. This is one reason why it is produced synthetically from morphine by modification. As codeine is the 3-0-methyl ether of morphine, the mono-O-methylation occurs in the acidic phenolic hydroxyl. Pholcodine is obtained by modification of morphine through alkylation with A-(chloroethyl)morpholine. Moreover, dihydrocodeine, hydro-morphone and heroine are also obtained from morphine through modifications. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Hydrocodone (Hycodan), oxycodone (Roxicodone), dihydrocodeine, hydromorphone (Dilaudid), and oxy-morphone (Numorphan) are derivatives of codeine and morphine. All are indicated for the relief of mild to severe pain or for their antipyretic effects they are often used in combination with nonopioid analgesics. The drugs vary in potency, but their pharmacological effects do not differ significantly from those of codeine or morphine. 

Rx with butalbital (Fiorinal) with codeine (Empirin) with dihydrocodeine and caffeine (Synalgos DC) wifh dipyridamole (Aggrenox) wifh oxycodone (Percodan) wifh propoxyphene (Darvon)... 

Related to codeine, dihydrocodeine is a rather weak analgesic, usually combined with other drugs and used as a headache suppressant, ft is often, however, prescribed for postoperative pain, dyspnea, and as an antitussive. Dihydrocodeine is twice as potent as codeine. 

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