Morphine derivative

Kotick s group have studied a number of dihydromorphinone derivatives (3) with N-CPM and N-CBM substituents.(32,33) The parent compounds have dual actions, the CPM member being the more potent antagonist and the CBM 

R Ring C substituent Analgesic ED5Q ° Antagonist ED5Q b 

8-[3H]naloxone specific activity 40 Ci/mmol ( = 97% pure) after tic or partition chromatography 6 

Summary of Effects of Some Opioids in Isolated Tissue Preparations  

Comparisons with morphine relate to agonist activity, others to antagonist properties 

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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. ... 

Thehaine stands at the other end of the series from morphine and is a convulsant poison rather than a narcotic (see table, p. 261). Hildebrandt states that it excites the reflexes of cold-blooded animals but in dogs it exerts a narcotic and anti-emetic effect resembling that of morphine rather than that of chloromorphide. The alkaloid is scarcely used in medicine as such, but is a primary material for the preparation of certain of the modern morphine derivatives, such as hydroxydihj dro-codeinone and methyldihydromorphinor.e. 

Transdermal patches are applied to the skin. The drug is mixed with the adhesive for the patch, and so it lies next to the skin. The skin can readily absorb many chemicals and so can absorb drugs such as nitroglycerin (for heart disease), morphine derivatives (for constant, severe pain), estrogen (for hormone replacement therapy), or nicotine (for easing symptoms that result when a patient stops smoking). 

Opiate A drug related to morphine, derived from opium. 

A useful introduction of the 14-hydroxyl substituent by co-catalyzed oxidation of certain morphine derivatives with air (oxygen) has been patented by Linders, a former student of the Delft alkaloid group, and Vrijhof (Organon/Diosynth) [29]. 

Visky, D., Kraszni, M., Hosztafi, S., and Noszal, B. (2000). HPCE analysis of hydrolysing morphine derivatives. Quantitation of decomposition rate and mobility. Chromatographia 51, 294-300. 

U-50488 has not only been a useful biological lead - its chemical structure, which is apparently unrelated to any of the classical morphine derivatives, has been used as the starting point for several drug discovery programmes. This has led to several publications and patents, particularly during the period 1989-1990, and these are discussed in this section. 

A crystallographic study of (Vila) (R = Me) has confirmed the overall structural resemblance of the endo-ethenothebaines and morphine [49] the former may be regarded as morphine derivatives in which the 6 and 14 carbon atoms of ring C are bridged by a bimethylene chain. This bicyclic feature lies... 

The present study has shown that enkephalin binds to PS in a pH-dependent fashion. The binding most likely involves the NHa group of the tyrosine residue of enkephalin and the CO2 group of PS. We have measured for the interaction and find it to be of the order of 5 x 10 M ("pH" 6.3) which is much weaker than the interaction of PS with morphine derivatives. Upon binding of enkephalin to PS the correlation time for internal motion in the backbone of the peptide increases by at least one order of magnitude (from 7.0 x 10" sec rad" ). The Ti of the bound peptide... 

It is worth mentioning that iV-allylic substitution in a number of morphine derivatives, as a rule, leads to antagonistic properties. Naloxone is a few times stronger than nalorphine as an antagonist. It blocks opiate receptors. It eliminates central and peripheral action of opioids, including respiratory depression. Naloxone is used upon overdose of narcotic analgesics.Synonyms for this drug are narkan, talwin, and others. 

For centuries opium was used for both medicinal and recreational purposes. Derived from the poppy Papaver somniferum, it contains numerous opiates, the primary one of which is morphine. The term opiate has largely been replaced by opioid, which represents all compounds with morphinelike activity and includes morphine, morphine derivatives, and peptides. Opiate is used to refer to morphinelike drugs derived from the plant and structurally similar analogues. These drugs are frequently referred to as narcotics, a Greek term for stupor, which is scientifically obsolete. Even in its early history, opium presented a problem when it was smoked or taken orally. The introduction of the hypodermic needle and syringe, however, drastically enhanced the euphoric properties of opioids and thereby altered their abuse liability. In addition, the synthesis of heroin resulted in an opioid that was more potent than morphine and ideally suited for intravenous administration. 

The pure opioid antagonist drugs naloxone,naltrexone, and nalmefene are morphine derivatives with bulkier substituents at the l l17 position. These agents have a relatively high affinity for - opioid binding sites. They have lower... 

Meanwhile, opium had been joined by other narcotics. Back in 1805 a German pharmacist s assistant had discovered how to isolate its main ingredient, morphine. A preparation of morphine is about 10 times as potent as raw opium. In 1832, another morphine derivative called codeine was isolated. By the 1850s, a more effective way to administer these powerful narcotics was developed—the hypodermic needle. During the American Civil War, battlefield surgeons had one effective way to relieve the pain of a shattered limb or punctured lung—an injection of morphine. Soldiers who survived their wounds after this treatment often became addicted to the drug. Morphine addiction was thus sometimes referred to as the soldier s disease. ... 

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... 

The introduction of heroin, although based on inaccurate observations and interpretation, undoubtedly influenced the trend and objectives of morphine research and marked the beginning of the search for an improved analgesic. During the 25 years after the introduction of heroin, other morphine derivatives were incorporated into medical practice some of which are still being used today. These include dihydrocodeine, differing from codeine only in the saturation of one double bond, hydrocodone... 

Pharmacokinetic properties Diamorphine is a lipophilic morphine derivative, which is well absorbed from the intestinal tract and rapidly penetrates into the CNS. It is already metabolized during the transport to the CNS yielding the active metabolites 6-acetylmorphine and morphine. The rapid brain access induces a quick onset of action and seems to be the reason for its high abuse potential (Inturrisi et al., 1984). 

The dextrorotatory isomer of 3-methoxy-A-methylmorphinan, a synthetic morphine derivative (Roinilar hydrobromide , Tusilan ) is employed exclusively as an antitussive agent. Its levorotary isomer (in the form of the 3-hydroxy tartrate) is described next. These compounds differ from morphine chemically in lacking the -O- bridge between carbons 4 and 5, the OH group at C6, and... 

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