Morphinans pharmacology

Work on the relationship between chemical structure and pharmacological activity of morphinans to 1966 has been reviewed by Hellerbach et al. s) and morphinans with antagonist properties were reviewed in 1973.(158) As is the case for 4,5-epoxymorphinans (Chapter 2) and benzomorphans (Chapter 4), molecular geometry is the major structure-biological activity influence, although the nature of the N-substituent imparts significant qualitative and quantitative variations in morphinan pharmacology. 

In Delft, several new morphinan-6,8-dienes have been studied, yielding Diels-Alder adducts with interesting pharmacological properties [30], In cases where the Diels-Alder reaction suffered from polymerization the use of microwave heating proved to be advantageous. 

A total of more than 20 total syntheses have been described which aim to generate the most important members of the morphinan-type alkaloids, morphine and codeine. These long-standing efforts in alkaloid synthesis have been primarily due to the exceptional pharmacological importance of both compounds, as the most efficacious therapies for pain and cough, respectively. 

A full account of chemical and pharmacological studies on morphinans to the mid-1960s is available/8 ... 

Morphinan-6-ones with hydroxyl groups at positions C-l, C-2, and C-4 have been prepared and their chemistry and pharmacology have been reviewed/501 These compounds will be discussed in a later section (p. 121). 

Substituents elsewhere in the C-ring may also endow morphinans with interesting pharmacological properties. 7-Alkylisomorphinans tend to be more... 

The capsules and stems of Papaver somniferum contain opiate alkaloids essential in medicine. They are classified into two groups, phenanthrene types (morphine, codeine, thebaine) and benzylisoquinoline types [papaverine and noscapine(narcotine)]. These two types of alkaloids show sharply specific pharmacological properties. It is noteworthy that morphinane alkaloids are formed from (-)-(/ )-reticuline, whereas most other alkaloids derive from (-l-)-(5)-re-ticuline 11). 

Gergely A, Gyimesi-Forras K, Horvath P, Hosztafi S, Kokosi J, Nagy PI, Szasz G, Szentesi A (2004) 6-Oxo-morphinane oximes pharmacology, chemistry and analytical application. Curr Med Chem 11 2555-2564... 

Morphinans. Only one of the two enantiomeric quaternary iodides, N-methyl-levorphanol exhibited specific opiate effects while the other enantiomer, N-methyl-dextrorphan was, as expected, inactive.In a series of 14-hydroxymorphinans, the epimeric isomorphinan (6) was a more potent antagonist than oxilorphan (5)(BC-2605).121 a review on the pharmacology of butorphanol (cyclobutyl analog of 5) has been published- - and clinical investigation of both the oral and parenteral forms is continuing.123-128... 

The benzomorphans thus far studied were all racemic. In view of the diverse pharmacological properties of the cycloalkylmethyl derivatives it was desirable that the compounds be resolved to ascertain wherein each action resided. Fortunately, for comparison with the morphine and morphinan nuclei we had available from Gates (8) the corresponding cyclopropylmethyl derivatives, 13 and 14. Table IV compares the analgesic antagonist activity of a group of cyclopropylmethyl derivatives with the resolved optically active dimethylallylbenzomorphan, 9. 

Butorphanol is a morphinan congener with a profile of actions similar to that of pentazocine. PHARMACOLOGICAL ACTIONS AND SIDE EFFECTS... 

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