Diacetylmorphine

Morphine is the principal alkaloid of opium. It acts both as a base and as a phenol and reacts to form methylmorphine (codeine ) and diacetylmorphine (diamorphine or heroin). 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

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. 

Dole VP, Nyswander MN A medical treatment for diacetylmorphine (heroin) addiction. JAMA 193 646-630, 1963... 

Heroin (diacetylmorphine) a highly lipophilic drug but has very weak or no affinity for opiate receptors. It penetrates the brain rapidly whereupon it is metabolised to morphine which then binds to the mu receptor. 

Figure 4.7b shows an example of a weak base, diacetylmorphine (heroin) [151]. The partition coefficient for the weak base is derived from... 

Chemical composition Diacetylmorphine Methylmorphine -Synthetic phenylpiperidines ... 

An example of particular importance is heroin (3,6-diacetylmorphine, 7.47). Following i.v. administration to human subjects, most of the dose was... 

More than 30 alkaloids have been identified in opium (Robbers et al. 1996). The most relevant are morphine (4-21%), codeine (0.8-2.5%), noscapine (4-8%), papaverine (0.5-2.5%), and thebaine (0.5-2%) (figure 8.4). Other opium alkaloids include narceine, protopine, laudanine, codamine, cytopine, lanthopine, and meconidine. Numerous other opioids have been synthesized from opium alkaloids. Among them is heroin, or diacetylmorphine. 

The basic structure of morphine (Fig. 26.1) can be altered in rather minor ways that drastically change the effects of the drug. Acetylation of the hydroxyl groups leads to the synthesis of heroin (diacetylmorphine). 

Esters (eg, heroin, remifentanil) are rapidly hydrolyzed by common tissue esterases. Heroin (diacetylmorphine) is hydrolyzed to monoacetylmorphine and finally to morphine, which is then conjugated with glucuronic acid. 

There are other substrates for the enzyme such as diacetylmorphine and substance P, and other variants have been described, some of which may lack enzymic activity. 

The earliest attempts to develop a non-dependence-inducing morphine derivative resulted in the preparation of heroin (3,6-diacetylmorphine) by acetylation of morphine (Wright, 1874, Dreser, 1898). The potency of heroin was soon recognized. It underwent more investigation than any other product of the time, and was introduced into clinical medicine in 1898. Reports of its reduced respiratory depression and dependence liability were soon shown to be unfounded, but its analgesic effects in animals and man (twice morphine) were confirmed. Pharmacological examination of acyl derivatives of morphine showed that... 

Synthesis Diacetylmorphine (Heroin) is demethylated with cyanogene bromide and hydrolyzed to normorphine, which is alkylated to ally bromide (, Weijlard and Erickson (Merck Co.), 1944 Weijlard (Merck Co), 1959 Klee-mann et al. 1999). 

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