Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The compound 9-beta-hydroxy-hexahydrocannabinol [(-)-9 beta-OH-HHC] was designed to fit a combined theoretical profile of an analgesic cannabinoid (equatorial alcohol at C-9, phenol at C-1 and a C-3 side chain) with reduced psychoactivity (axial C-9 substituent which protrudes into the alpha face). (-)-9 beta-OH-HHC was synthesized by the addition of methyl Grignard to 9-oxo-11-nor-HHC. Its alpha epimer was obtained by the regiospecific epoxide ring opening of 9 alpha, 10 alpha-epoxy-HHC acetate. (-)-9 beta-OH-HHC and (-)-9 alpha-OH-HHC were each evaluated in a battery of tests in mice and were found to be 10-25 times less potent than (-)-trans-delta 9-tetrahydrocannabinol (delta 9-THC) in all tests including the tail flick test for antinociception (analgesia). Molecular mechanics calculations [MMP2(85)] revealed that, in the global minimum energy conformation of (-)-9 beta-OH-HHC, the axial methyl at C-9 protrudes into the alpha face of the molecule, while the axial hydroxyl at C-9 in (-)-9 alpha-OH-HHC protrudes into this same face. These calculations also identified a higher energy carbocyclic ring (twist) conformer of each in which there is no protrusion of a C-9 substituent of the carbocyclic ring into the alpha face. The minimal activity of both compounds is attributed to these higher energy forms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A rational search for the separation of psychoactivity and analgesia in cannabinoids. 180 40

Blood coagulation and fibrinolysis were studied in 20 premenopausal women undergoing abdominal hysterectomy under general anaesthesia (GA) or high epidural analgesia (EDA). As expected, the adrenocortical stress response was suppressed in the EDA group. The Factor VIII complex (F VIII:C, F VIII R:Ag = von Willebrand factor), known to be related to adrenocortical activity and/or vessel wall reactivity, was found to increase less in the EDA group. With regard to all the other variables analysed there were no significant differences between the groups. With both anaesthetic procedures activation of coagulation could be demonstrated by a decrease in prekallikrein, F X and antithrombin as well as by an increase in fibrinopeptide A levels. A decrease in plasminogen and alpha 2-antiplasmin suggested activation of the fibrinolytic system and a decrease in prekallikrein and kallikrein inhibition activity (C-1-esterase inhibitor) an activation of the kallikrein system. In this study only the differences in F VIII complex could explain the previously reported higher thromboembolic frequency after GA as compared to EDA.
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PMID:Per- and postoperative changes in coagulation and fibrinolytic variables during abdominal hysterectomy under epidural or general anaesthesia. 373 76