Early medical use of cannabis stetrics is cited in several medical publications, one of which4 in... more Early medical use of cannabis stetrics is cited in several medical publications, one of which4 indicates that C. sativa had the remarkable power to increase the force of uterine contractions, concomitant with a significant reduction of labour pain.
Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were pre... more Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB 1 and CB 2), as well as for activation of CB 1-and CB 2-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB 1 and CB 2 (K i values of 38.0 (7.2 and 26.6 (5.5 nM, respectively) and to inhibit CB 1-mediated adenylylcyclase with an EC 50 of 58.1 (6.2 nM but to cause only 20% inhibition of CB 2-mediated adenylylcyclase at 10 µM. It behaves as a specific, though not potent, CB 2 antagonist. 11-Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB 1 and CB 2 (K i values of 100 (50 and 200 (40 pM; EC 50 of adenylylcyclase inhibition 56.2 (4.2 and 207.5 (27.8 pM, respectively).
La presente invention concerne des composes de formule generale (1) analogues, non hydrolysables,... more La presente invention concerne des composes de formule generale (1) analogues, non hydrolysables, de cannabinoides endogenes, qui sont des agents therapeutiques plus puissants en raison de leur plus grande stabilite, par exemple, par rapport a la scission hydrolytique dans le tractus gastro-intestinal. Les analogues de cannabinoides de l'invention possedent une valeur therapeutique, ce qui permet la preparation de compositions pharmaceutiques comprenant, en tant que principe actif, une quantite efficace, sur le plan therapeutique, d'au moins un des composes de l'invention. De telles compositions peuvent etre utilisees comme anti-inflammatoire, antiasthmatique, analgesique, hypotenseur, antiemetique ou antispasmodique, ou pour le traitement et/ou pour la prevention de glaucome ou de migraine, ou pour le traitement des symptomes de sclerose en plaques et de stimulation de l'humeur.
The 1,l-dimethylheptyl (DMH) homologue of 7-hydroxy-A6-tetrahydrhydrocannabinol (3) is the most p... more The 1,l-dimethylheptyl (DMH) homologue of 7-hydroxy-A6-tetrahydrhydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5'-(l,l-dimethylheptyl)-7hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (S), depending on the catalysts and conditions used. Compound 7 discriminates for A'-THC (2) in pigeons (EDm = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (l), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor. 8 DMH = 1 .l-dimethylheptyl A'-tetrahydrocannabinol (A'-THC) (2). An additional
Proceedings of the National Academy of Sciences of the United States of America, Dec 7, 1999
Two cannabinoid receptors have been identified: CB1, present in the central nervous system (CNS) ... more Two cannabinoid receptors have been identified: CB1, present in the central nervous system (CNS) and to a lesser extent in other tissues, and CB2, present outside the CNS, in peripheral organs. There is evidence for the presence of CB2-like receptors in peripheral nerve terminals. We report now that we have synthesized a CB2-specific agonist, code-named HU-308. This cannabinoid does not bind to CB1 (Ki > 10 M), but does so efficiently to CB2 (Ki ؍ 22.7 ؎ 3.9 nM); it inhibits forskolin-stimulated cyclic AMP production in CB2-transfected cells, but does so much less in CB1-transfected cells. HU-308 shows no activity in mice in a tetrad of behavioral tests, which together have been shown to be specific for tetrahydrocannabinol (THC)-type activity in the CNS mediated by CB1. However, HU-308 reduces blood pressure, blocks defecation, and elicits anti-inflammatory and peripheral analgesic activity. The hypotension, the inhibition of defecation, the anti-inflammatory and peripheral analgesic effects produced by HU-308 are blocked (or partially blocked) by the CB2 antagonist SR-144528, but not by the CB1 antagonist SR-141716A. These results demonstrate the feasibility of discovering novel nonpsychotropic cannabinoids that may lead to new therapies for hypertension, inflammation, and pain.
Comparison of relative bioluminescence production by V. harveyi MM77 (AI-1-, AI-2-, sensor-1+, se... more Comparison of relative bioluminescence production by V. harveyi MM77 (AI-1-, AI-2-, sensor-1+, sensor-2+) with different HU-210 concentrations when simultaneously supplemented with exogenous AI-1 and AI-2 from V. harveyi mutant strains MM30 (AI-1+, AI-2-) and BB152 (AI-1-, AI-2+) respectively, presented as area under the curve. Presented data are means and SD of three independent experiments, each performed in triplicate. *P
This paper reports results with the new sensitivity verification for ultra high frequency (UHF) p... more This paper reports results with the new sensitivity verification for ultra high frequency (UHF) partial discharge (PD) detection applied to three-phase SF/sub 6/ gas-insulated substations (GIS) for rated voltages up to 170 kV. The procedure was developed by CIGRE WG 15/33.03.05. The aim is to examine the practical use of the proposed procedure and to investigate its extension to an unconventional sensor type. UHF PD measurements were carried out on a typical GIS section via potential grading electrodes. Derived results demonstrate the ability of these already built-in devices to serve as UHF sensors, to replace additional sensors sufficiently, and to make further design efforts unnecessary, if UHF diagnostics are required. Measurements, the experimental setup and the adequate test-vessel are described. The sensitivity of the new sensor is compared to the sensitivity of the IEC 60270 method and to other UHF sensors. Results concerning the detection of characteristic defects demonstra...
Photooxidation des Dibromaddukts (II) aus dem Epoxyannulen (I) gibt glatt das Trioxid (III) (kein... more Photooxidation des Dibromaddukts (II) aus dem Epoxyannulen (I) gibt glatt das Trioxid (III) (keine Ausbeuteangabe), aus dem die Verbindung (IV) gewonnen wird.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical mariju... more Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.
1998 Annual Report Conference on Electrical Insulation and Dielectric Phenomena (Cat. No.98CH36257)
Digital systems for partial discharge (pd)-measurement allow the detection of pd characteristics ... more Digital systems for partial discharge (pd)-measurement allow the detection of pd characteristics according to IEC 270 as well as the classification of pd-sources. For pd-fault recognition a neural network based on the back propagation algorithm was implemented in C++ on a personal computer with Windows 95. The program uses input data files from PRPDA (phase resolved pd analysis) system ICM
Early medical use of cannabis stetrics is cited in several medical publications, one of which4 in... more Early medical use of cannabis stetrics is cited in several medical publications, one of which4 indicates that C. sativa had the remarkable power to increase the force of uterine contractions, concomitant with a significant reduction of labour pain.
Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were pre... more Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB 1 and CB 2), as well as for activation of CB 1-and CB 2-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB 1 and CB 2 (K i values of 38.0 (7.2 and 26.6 (5.5 nM, respectively) and to inhibit CB 1-mediated adenylylcyclase with an EC 50 of 58.1 (6.2 nM but to cause only 20% inhibition of CB 2-mediated adenylylcyclase at 10 µM. It behaves as a specific, though not potent, CB 2 antagonist. 11-Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB 1 and CB 2 (K i values of 100 (50 and 200 (40 pM; EC 50 of adenylylcyclase inhibition 56.2 (4.2 and 207.5 (27.8 pM, respectively).
La presente invention concerne des composes de formule generale (1) analogues, non hydrolysables,... more La presente invention concerne des composes de formule generale (1) analogues, non hydrolysables, de cannabinoides endogenes, qui sont des agents therapeutiques plus puissants en raison de leur plus grande stabilite, par exemple, par rapport a la scission hydrolytique dans le tractus gastro-intestinal. Les analogues de cannabinoides de l'invention possedent une valeur therapeutique, ce qui permet la preparation de compositions pharmaceutiques comprenant, en tant que principe actif, une quantite efficace, sur le plan therapeutique, d'au moins un des composes de l'invention. De telles compositions peuvent etre utilisees comme anti-inflammatoire, antiasthmatique, analgesique, hypotenseur, antiemetique ou antispasmodique, ou pour le traitement et/ou pour la prevention de glaucome ou de migraine, ou pour le traitement des symptomes de sclerose en plaques et de stimulation de l'humeur.
The 1,l-dimethylheptyl (DMH) homologue of 7-hydroxy-A6-tetrahydrhydrocannabinol (3) is the most p... more The 1,l-dimethylheptyl (DMH) homologue of 7-hydroxy-A6-tetrahydrhydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5'-(l,l-dimethylheptyl)-7hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (S), depending on the catalysts and conditions used. Compound 7 discriminates for A'-THC (2) in pigeons (EDm = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (l), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor. 8 DMH = 1 .l-dimethylheptyl A'-tetrahydrocannabinol (A'-THC) (2). An additional
Proceedings of the National Academy of Sciences of the United States of America, Dec 7, 1999
Two cannabinoid receptors have been identified: CB1, present in the central nervous system (CNS) ... more Two cannabinoid receptors have been identified: CB1, present in the central nervous system (CNS) and to a lesser extent in other tissues, and CB2, present outside the CNS, in peripheral organs. There is evidence for the presence of CB2-like receptors in peripheral nerve terminals. We report now that we have synthesized a CB2-specific agonist, code-named HU-308. This cannabinoid does not bind to CB1 (Ki > 10 M), but does so efficiently to CB2 (Ki ؍ 22.7 ؎ 3.9 nM); it inhibits forskolin-stimulated cyclic AMP production in CB2-transfected cells, but does so much less in CB1-transfected cells. HU-308 shows no activity in mice in a tetrad of behavioral tests, which together have been shown to be specific for tetrahydrocannabinol (THC)-type activity in the CNS mediated by CB1. However, HU-308 reduces blood pressure, blocks defecation, and elicits anti-inflammatory and peripheral analgesic activity. The hypotension, the inhibition of defecation, the anti-inflammatory and peripheral analgesic effects produced by HU-308 are blocked (or partially blocked) by the CB2 antagonist SR-144528, but not by the CB1 antagonist SR-141716A. These results demonstrate the feasibility of discovering novel nonpsychotropic cannabinoids that may lead to new therapies for hypertension, inflammation, and pain.
Comparison of relative bioluminescence production by V. harveyi MM77 (AI-1-, AI-2-, sensor-1+, se... more Comparison of relative bioluminescence production by V. harveyi MM77 (AI-1-, AI-2-, sensor-1+, sensor-2+) with different HU-210 concentrations when simultaneously supplemented with exogenous AI-1 and AI-2 from V. harveyi mutant strains MM30 (AI-1+, AI-2-) and BB152 (AI-1-, AI-2+) respectively, presented as area under the curve. Presented data are means and SD of three independent experiments, each performed in triplicate. *P
This paper reports results with the new sensitivity verification for ultra high frequency (UHF) p... more This paper reports results with the new sensitivity verification for ultra high frequency (UHF) partial discharge (PD) detection applied to three-phase SF/sub 6/ gas-insulated substations (GIS) for rated voltages up to 170 kV. The procedure was developed by CIGRE WG 15/33.03.05. The aim is to examine the practical use of the proposed procedure and to investigate its extension to an unconventional sensor type. UHF PD measurements were carried out on a typical GIS section via potential grading electrodes. Derived results demonstrate the ability of these already built-in devices to serve as UHF sensors, to replace additional sensors sufficiently, and to make further design efforts unnecessary, if UHF diagnostics are required. Measurements, the experimental setup and the adequate test-vessel are described. The sensitivity of the new sensor is compared to the sensitivity of the IEC 60270 method and to other UHF sensors. Results concerning the detection of characteristic defects demonstra...
Photooxidation des Dibromaddukts (II) aus dem Epoxyannulen (I) gibt glatt das Trioxid (III) (kein... more Photooxidation des Dibromaddukts (II) aus dem Epoxyannulen (I) gibt glatt das Trioxid (III) (keine Ausbeuteangabe), aus dem die Verbindung (IV) gewonnen wird.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical mariju... more Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.
1998 Annual Report Conference on Electrical Insulation and Dielectric Phenomena (Cat. No.98CH36257)
Digital systems for partial discharge (pd)-measurement allow the detection of pd characteristics ... more Digital systems for partial discharge (pd)-measurement allow the detection of pd characteristics according to IEC 270 as well as the classification of pd-sources. For pd-fault recognition a neural network based on the back propagation algorithm was implemented in C++ on a personal computer with Windows 95. The program uses input data files from PRPDA (phase resolved pd analysis) system ICM
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