Morphine as analgesic

Substitution at C-6 was not necessary for good levels of analgesic activity, for desomorphine (83, R = Me) was 10 times more potent than morphine. However, some 6-azido-4,5-epoxymorphinans (e.g., 89) were 50 x morphine as analgesics in humans, and although the same level of activity was seen in corresponding 14-OH derivatives, the fact that the presence of a 14-OH did not increase the level of potency indicates that in this case the 6- and 14-substituents affect receptor binding differently. 

List T, Tegelberg A, Haraldson T, Isacsson G. Intra-articular morphine as analgesic in temporomandibnlar joint arthralgia/osteoarthritis. Pain 2001 94 275-282. 

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

The l -form is much the more potent, being two to seven times more potent than morphine as an analgesic. It is called levo-nantradol. 

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Codeine (12) and morphine (13), both major active constituents of opium resin, the dried latex from the immature fruits of Papaver som-niferum L., are pharmacologically important drugs as analgesic agents with considerable use today. Like other opiates, morphine and codeine... 

Initial therapy- There has been no evaluation of CR/ER/SR morphine as an initial opioid analgesic in the management of pain. Because it may be more difficult to titrate a patient to adequate analgesia using a CR/ER/SR morphine, it is ordinarily advisable to begin treatment using an immediate-release morphine formulation. 

Morphine and narceine are active on / -opiate and K-receptors. They are also known as analgesic agents. These alkaloids may be used as pain relievers. Narceine is also known to be used in the treatment of a cough. 

The most important other opium alkaloid is codeine. In contrast to morphine, codeine has a high oral-parenteral potency ratio due to less first-pass metabolism. Codeine is considered a prodrug, since it is metabolised in vivo to the primary active compounds morphine and codeine-6-glucuronide. Approximately 10% is demethylated to morphine. The analgesic effect of codeine is due to the formation of these metabolites as codeine itself has a very low affinity for opioid receptors. The half-life of codeine in plasma is 2 hours. 

Codeine is a close chemical relative of morphine, differing in only one chemical group. Once administered, codeine is actually metabolized by enzymatic action, and its actions mimic those of morphine. Codeine is used primarily as a cough suppressant, although it certainly also possesses significant analgesic properties (approximately one tenth those of morphine) as in the relief of pain from toothache. 

Analgesic efficacy and clinical use Codeine (Honig and Murray, 1984) has a morphine-like action profile with analgesic and antitussive properties. As compared to morphine the analgesic potency is 5—1 Ofold lower. The compound is used for the treatment of mild to moderate pain and for cough inhibition (Eccles,1996). 

An alkaloid, epibatidin (173), has been isolated from skin of the Ecuadorian frog Epipedobates tricolor which exhibited a 200-fold potency compared with morphine as an analgesic in the Straub-tail test. Extracts from 750 frogs provided only 1 mg of the Straub-tail alkaloid. The researchers had to wait for a decade until more sensitive instruments... 

As you can see from Figure 23-1, alkaloids include compounds that may be classified as antimicrobial (quinine), as analgesics (morphine, codeine), as hallucinogens (mescaline, LSD), as stimulants (cocaine, atropine, caffeine),... 

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