Morphine as an analgesic

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. 

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... 

This situation became particularly acute with respect to the development of illicit analogs of fentanyl to derive heroin substitutes. Fentanyl is a synthetic opioid, a p-receptor agonist, and is about 100-200 times more potent than morphine as an analgesic. As with other narcotic analgesics, respiratory depression is the most significant acute toxic effect of the fentanyl derivatives. Fentanyl analogs can be 80-1000... 

Tramadol, however, is thousands of times less potent than morphine as an analgesic agent [18]. It is marketed in the racemic form, and each enantiomer has distinct pharmacological actions. The (+)-isomer is a weak MOP agonist, while the (-)-isomer inhibits neurotransmitter reuptake (norepinephrine and serotonin). The O-demethylated metabolite has improved opioid receptor affinity but is still much less potent (35-fold) than morphine. The ability for this metabolite to ameliorate the analgesic effects of tramadol has not been well studied and remains questionable. The drug has been used for decades in Europe, but was only recently introduced in the United States. It has a greater safety profile than morphine, and produces no respiratory depression or constipation. It is also claimed to be nonaddictive, but remains unscheduled. 

These compounds can then be readily converted into 7-azabicyclo[2.2.1]heptan-2-ones of type 1090 (Scheme 212), which have been shown to be useful precursors for the synthesis of the novel alkaloid epibatidine <1996JOC7189>. Epibatidine has been found to be 200-400 times more potent than morphine as an analgesic, and more importantly should prove to be useful for the preparation of its analogs with reduced toxicity. The approach with phenyl 1,2-propadienyl sulfone 1091 (R = S02Ph, R = H) proved to be more efficient and high yielding than the ester sequence and provided azabicycle 1090 in 19% overall yield (four steps). 

Subsequent animal tests indicated that butorphanol is about 4 times more potent than morphine as an analgesic and equivalent to nalorphine as an antagonist. Clinical evaluation shows that butorphanol is also an effective analgesic in man (approximately 5 times more potent than morphine), and the tartrate is now marketed as an injection (Stadol). In animals its PDC is low (less than that of pentazocine) as it is in man, and this fact and its ceiling rather than dose-related effect on respiration (see p. 414) are recommendations for clinical use of the drug.<5,64)... 

The 93-propyl levo Isomer (3c) was considerably more potent subcutaneously than morphine, while the 9oi-propyl levo Isomer (3d) was equipotent with morphine as an analgesic. None of the optical isomers suppressed withdrawal signs in monkeys the 9f5-propyl levo isomer exacerbated the withdrawal syndrome, indicating that it possesses some narcotic antagonist activity.The most active compound (4) of six homobenzomorphans was as potent subcutaneously as morphine (measured by pressure stimuli on mouse tail).115,116 Simplified procedures for the synthesis of the 6,7-benzomor-phan series have been described.117,118 Several 11-hydroxy and 11-alkoxy-2,6-methano-3-benzazocines display as potent analgesic and narcotic antagonist activity as cyclazocine.H ... 

It is a benzomorphan analogue about 40 times more potent than morphine as an analgesic and about 100 times more potent than nalorphine as an antagonist. The addiction potential of this drug seems to be much less than that of morphine. It has been used clinically to treat diamorphine or morphine addicts. 

It is a potent narcotic analgesics having actions quantitatively comparable to morphine though slightly less potent than morphine as an analgesic. Besides, it exerts sedation and antitussive properties. It also helps in the temporary maintenance and treatment of dependence on narcotic drugs, because its withdrawal syndrome has slow onset and much less intense than mrophine. 

The first attempts to find a substance with morphine s benefits but without its side effects involved minor modification of its structure. Acetylation with acetic anhydride gave its diacetyl derivative heroin, which is a good analgesic with less of a respiratory depressant effect than morphine. But heroin is severely addictive, and its abuse has become a serious problem. Partial methylation of morphine gave codeine, which is useful as an antitussive (anticough) agent. Unfortunately, it is less than one-tenth as effective as morphine as an analgesic. 

Unfortunately, it is less that one-tenth as effective as morphine as an analgesic. 

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