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YANNICK GOUMON Y COLS. AN. R. ACAD. NAC. FARM.

in (47)]. The longer-lasting action of M6G coupled with its lower
incidence of adverse reactions make it a very promising analgesic. A
number of clinical studies are currently underway to compare the
analgesic activities of M6G and morphine in the management of
postoperative pain (48).

2. ENDOGENOUS MORPHINE

a) History

In 1903, a French scientist, Dr. Mavrojannis, observed that, when
he injected morphine into rats, they presented symptoms similar to
those of a cataleptic attack (49). He hypothesised that an endogenous
substance similar to morphine was present in the rat brain. However,
it was necessary to wait for the improved detection methods of the
1970’s —notably radioimmunoassay (RIA)— before a compound
related to morphine could be detected in the brains of mice, rabbits
and cats (50). This substance was not sensitive to proteases and had
the same pharmacological receptor-binding profile as morphine. It
was first called Morphine-Like Compound (MLC) (50) and was
isolated from human cerebrospinal fluid (CSF), urine and brain
extracts [prepared from patients who had never been given morphine
(51)]. Subsequently, large quantities of MLC were purified from
rabbit, rat and toad (Bufo marinus) epidermal tissue (52, 53). In
1985, Goldstein et al. purified a morphine-related compound from
an extract of bovine hypothalamus and adrenal glands (54). Using
chromatography and nuclear magnetic resonance (NMR), they
showed that the substance was indeed morphine, with a structure
identical to that of the plant molecule (54).

Subsequent experiments showed that this alkaloid could be found
in the neural and immune cells of invertebrates (55). Endogenous
alkaloids also seem to be produced by certain parasites, morphine
having been detected in both Schistosoma mansoni (56) and Ascaris
suum (57). Some scientists remained sceptical and believed that this
morphine could have come from food: morphine had been detected
in many plants (including hay and lettuce) as well as in cow’s and
human breast milk, at concentrations of between 200 and 500 ng/L
(58). Experiments in livestock reared in strictly morphine-free

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