Narcotics morphine

The PE spectra of some other alkaloids like methadone and the opiate narcotics morphine, codeine and heroin have been investigated by Klasinc and coworkers95. Also in this study structure-activity relationships based on IPs were sought but not found. Since the interaction of the drug molecule with the receptor is highly specific, it is not unreasonable that the molecular rather than the electronic structure is more important for the physiological activity. 

The use of natural products as medicine has invoked the isolation of active compounds the first commercial pure natural product introduced for therapeutic use is generally considered to be the narcotic morphine (1), marketed by Merck in 1826, and the first semi-synthetic pure dmg aspirin (2), based on a natural product salicin (3) isolated from Salix alba, was introduced by Bayer in 1899. This success subsequently led to the isolation of early dmgs such as cocaine, codeine, digitoxin (4), quinine (5), and pilocarpine (6), of which some are still in use. ... 

Morphinans (compactly fused Phe, C6, C5N, C6 and C40 rings) Codeine (opium-derived addictive, analgesic, antitussive, spasmolytic narcotic) morphine (opium-derived addictive, analgesic, antitussive, sedative, spasmolytic narcotic heroin is the semisynthetic diacetate) thebaine (non-analgesic, toxic, convulsant narcotic and semi-synthesis precursor of the anti-addiction drug naltrexone). 

O-R ligand (opiate agonist thence inhibits AC per Gai) [analgesic, narcotic (= Morphine), neurotoxic]... 

Figure 2.3 Dextromethorphan 6, the unnatural enantiomer of a narcotic morphine analog, is an antitussive drug. The antidiarrhea drug loperamide 7 and the neuroleptic drug haloperidol 8 also resulted from structural modification of morphine. The morphine antagonist nalorphine 9 differs from the opioid agonist morphine 3 (Figure 2.2) only by having an N-allyl group instead of the N-methyl group.

Beginning in 1985, a series of patents was issued for the use of ibogaine as a rapid means of interrupting addiction to narcotics (morphine and heroin) (3), cocaine and amphetamine (4), alcohol (5), nicotine (6) and polydrug dependency syndrome (35). These patents claim that an oral or rectal dose of ibogaine (4-25 mg/kg) interrupts the dependence syndrome, allowing patients to maintain a drug-free lifestyle for at least 6 months. 

The male client diagnosed with a brain tumor tells the clinic nurse that he has been having seizures more frequently. The client is taking the anticonvulsant phenytoin (Dilantin), the narcotic morphine sulfate (Roxanol), the analgesic acetaminophen (Tylenol), and the antianxiety medication alprazolam (Xanax). Which question about the client s medications should the nurse ask next ... 

The narcotic morphine IVP to the client who has pleuritic chest pain. 

The narcotic morphine IVP to the client who has pleuritic chest pain that is a 7 on a 1-10 pain scale. 

However, it s only in the nineteenth century that scientists isolated active components from various medicinal plants. The first commercial pure natural product introduced for therapeutic use is considered to be the narcotic morphine, in 1826. Natural products still play a very important role in modern medicine in fact, they are increasingly the primary sources in drug discovery. 

Analgesics/ narcotics—morphine Mydriatics—atropine Miotics—pilocarpine Hypertensives—ephedrine... 

Narcotic Morphine Heroin Codeine Methadone Fentanyl... 

Opium poppy (Papaver somniferum), producing a large number of alkaloids including the narcotics morphine and codeine, may be the prime example for a non-model plant on the... 

As with acyclic amines (Chapter 21), the (Lewis) basic nature of the alkaloids, in conjunction with their particular three-dimensional architecture, gives rise to often potent physiological activity. We have already noted some examples of this behavior in the narcotics morphine and heroin (Section 9-11), the psychoactive lysergic acid and LSD (Section 19-13), and the antibiotic penicillins (Real Life 20-2). 

Classes of drugs include hallucinogens (mostly derivatives of phenethylamine or trypt-amine), narcotics (morphine and derivatives), stimulants (cocaine, amphetamines), and depressants (barbiturates, benzodiazepines). 

Figure 3.4 Structures of selected narcotics morphine (1), heroin (2), pethidine (3), buprenorphine (4), and fentanyl (5).

The Opiates. The International Narcotics Control Board—Vienna, tracks the tick production of narcotic dmgs and annually estimates world requkements for the United Nations. Thek most recent pubHcation (100) points out that more than 95% of the opium for Hcit medical and scientific purposes is produced by India and, in a declining trend, only about 600 t was utilized in 1988. This trend appears to be due to the fact that the United States, the largest user of opium for alkaloid extraction, reduced the amount of opium being imported from about 440 t in 1986 to 249 t in 1987 and 224 t in 1988. The United States used about 48 t of morphine (2, R = H) in 1988, most (about 90%) being converted to codeine (2, R = CH3) and the remainder being used for oral adrninistration to the terminally ill (about 2 t) and for conversion to other materials of minor commercial import which, while clearly alkaloid-derived, are not naturally occurring. 

Narcotic Antitussives. Since its isolation in 1832, codeine [76-57-3] (27) has been one of the most widely used and effective compounds for the treatment of cough. Though less potent than morphine [57-27-2] (28), it has become the reference against which most antitussives are measured. 

Modifications of the morphine skeleton have produced butorphanol [42408-82-2] (35) and drotebanol [3176-03-2] (36), which in animal models have demonstrated antitussive activity much greater than that of codeine (51,52). Butorphanol is also a potent analgetic of the narcotic antagonist type (51). Both compounds possess a unique 14-hydroxyl group. 

The synthesis of dextromethorphan is an outgrowth of early efforts to synthesize the morphine skeleton. /V-Methy1morphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-/V-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciUary activity, secretion of respiratory tract fluid, or respiration. 

Noscapine [128-62-1] (45) is the second most abundant alkaloid found in opium. Unlike most opium alkaloids, however, it has an isoquinoline rather than a phenanthrene ting system. Noscapine was first isolated in 1817 but its antitussive activity was not demonstrated pharmacologically until 1952 (63). Clinical studies have confirmed its effectiveness. It is not a narcotic and has a wide margin of safety when given orally. Death could be produced in rats only with doses > 800 mg/kg (64). Noscapine is isolated from the water-insoluble residue remaining after processing opium for the manufacture of morphine. 

A characteristic feature of the action of the opium alkaloids is their simultaneous depressing and exciting action on the central nervous system. In this respect there is no clear line of demarcation between the morphine group—morphine, codeine and thebaine—and the papaverine-narcotine group, and as the series is ascended in the order, morphine, papaverine, codeine, narcotine, thebaine, narcotic action diminishes and power of rellex stimulation increases until in thebaine a strychnine-like effect is exhibited. 

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. 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

Although this isoquinoline at first bears little structural resemblance to morphine (108), careful rearrangement of the structure (A) shows the narcotic to possess the benzylisoquinoline fragment within its framework. Indeed, research on the biogenesis of morphine has shown that the molecule is formed by oxidative coupling of a phenol closely related to papaverine. 

Narcotic analgesic. A drug that alleviates pain by interacting with the morphine receptor. 

Narcotic antagonist. A drug that selectively blocks the actions of morphine-like compounds. 

Examples narcotics such as meperidine, methadone, morphine, oxycodone amphetamines and barbiturates... 

Morphine, when extracted from raw opium and treated chemically, yields the semisynthetic narcotics hydromorphone, oxymorphone, oxycodone, and heroin. Heroin is an illegal narcotic in the United States and is not used in medicine. Synthetic narcotics are those man-made analgesics with properties and actions similar to the natural opioids. Examples of synthetic narcotic analgesics are methadone, levorphanol, remifen-tanil, and meperidine Additional narcotics are listed in the Summary Drug Table Narcotic Analgesics. 

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