Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1997-09-30
1999-11-23
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514676, 514679, 514716, 544107, 562555, 564152, A61K 3116, C07C23301, C07C23570, C07D26530
Patent
active
059901705
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a therapeutic method for the treatment of diseases connected with the modulation of the cannabinoid peripheral receptor, comprising administering amidic derivatives of mono and bicarboxylic acids with substituted aminoalcohols or aminoethers.
PRIOR ART DISCLOSURE
Cannabinoids are a specific class of psychoactive compounds present in Indian cannabis (Cannabis sativa), including about 60 different molecules, the most representative being cannabinol, cannabidiol and several isomers of tetrahydrocannabinol. Knowledge of the therapeutic activity of cannabis dates back to the ancient dynasties in China, where, already 5,000 years ago, cannabis was used for the treatment of asthma, migraine and some gynaecologic disorders. Said use later bacame so established that about in 1850 cannabis extracts were included in the US Pharmacopaeia and remained therein until 1947.
Cannabinoids are able to cause different effects at the level of various systems and/or organs; the most important effects occur on the central nervous system and on the cardiovascular system. In fact, they are able to affect mood, memory, motor coordination and cognition, and they increase heart rate and variate the systemic arterial pressure. Furthermore, it is well known the capability of cannabinoids to reduce intraocular pressure and to affect the respiratory and endocrine systems (L. E. Hollister, Health Aspects of Cannabis, Pharmacological Reviews, 38, 1-20, 1986). More recently, it was found that they suppress the cellular and humoral immune response and have antiinflammatory properties (A. W. Wirth et al., Antiinflammatory Properties of Cannabichromene, Life Science, 26, 1991-1995, 1980). However, the therapeutic use of cannabis is controversial both due to its relevant psychoactive effects, causing dependence and addiction, and to the manifold side effects that have not yet been completely clarified (L. E. Hollister, 1986, reference cited).
Notwithstanding the well established use of cannabis over the centuries, the mechanism of the effects of cannabinoids has been unknown until very recently. It was only in 1990 that Matsuda and collaborators identified and cloned a cannabinoid receptor belonging to the G-protein-coupled family of receptors; CB1 is coupled to G1 to inhibit adenilate cyclase activity and to a partussis-sensitive G protein to regulate Ca.sup.2+ currents. Said receptor was found to be mainly located in the brain, in neural cell lines and only to a lesser extent at a peripheral level; therefore, in view of its localization, it was called Central Receptor (CB1) (Matsuda et al., Structure of a cannabinoid receptor and functional expression of the cloned cDNA, Nature, 346: 561-564, 1990). The discovery of a receptor led to assume the existence of a specific endogenous ligand.
In fact, subsequent research led to the isolation from pig brain of a substance able to exert an agonist action, i.e. capable of binding to the cannabinoid central receptor in a competitive way. Said substance was identified by structural investigation and by comparison with the synthetic product and was found to be an amidic derivative of arachidonic acid, and more particularly arachidonylethanolamide, later called anandamide. The pharmacological characterization of said molecule provided evidence that anandamide possesses a profile of activity which is similar to, though less potent than, .DELTA.9-THC (tetrahydrocannabinol with a double bond in position 9), and is capable of mimicking the psychoactive effects thereof. Said evidences led to the conclusion that anandamide is the endogenous ligand of the cannabinoid central receptor (C. C. Felder et al., Anandamide, an Endogenous Cannabimimetic Eicosanoid, Binds to the Cloned Human Cannabinoid Receptor and Stimulates Receptor-mediated Signal Tranisduction, FNAS, 90, 7656-7660, 1993; P. B. Smich et al., The Pharmacological Activity of Anandamide, a Putative Endogenous Cannabinoid, in Mice, J. PET, 270, 219-227, 1994).
Subsequent researches brought about
REFERENCES:
Munro et al., Nature, vol. 365 pp. 61-65, 1993.
Facci et al., Proc. Natl. Acad. Sci. USA vol. 92 pp. 3376-3380, 1995.
della Valle Francesco
Leon Alberta
Lorenzi Silvana
Marcolongo Gabriele
Lifegroup S.P.A.
Richter Johann
Solola Taofiq A.
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