PubMed · 14026527
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T J DEKORNFELD, T M FRAZIER, L LASAGNA. 1963-03-23. Analgesic compounds.. https://doi.org/10.1001/jama.1963.03700120109025
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Homoepiboxidine (3) and the corresponding N-methyl (4) and N-benzyl (5) derivatives were prepared from a 6beta-carbomethoxynortropane (8). Affinities and functional activities at neuromuscular, central neuronal and ganglionic-type nicotinic receptors were compared to those of epibatidine 1, and epiboxidine 2. Homoepiboxidine had equivalent affinity/activity to epiboxidine at neuromuscular, neuronal alpha4beta2, and most alpha3-containing ganglionic-type nicotinic receptors. The N-substituted derivatives showed reduced affinity/activity at most receptor subtypes. Replacement of the methylisoxazole moiety of 3 and 4 with a methyloxadiazole moiety provided analogues 6 and 7, which had greatly reduced affinity/activity in virtually all assays at nicotinic receptors. Marked analgetic activity in mice occurred at the following ip doses: epibatidine 10 microg/kg; epiboxidine 25 microg/kg; homoepiboxidine 100 microg/kg; N-methylhomoepiboxidine 100 microg/kg; the methyloxadiazole (6) 100 microg/kg. The time course at such ip doses was significantly longer for homoepiboxidine 3 with marked analgesia still manifest at 30 min post-injection. Epiboxidine and the homoepiboxidines were less toxic than epibatidine.
Pain concerns more than 50% of the children cared in the emergency unit. After evaluation, it has to be cured with drugs adapted to its level and its origin. Residual pain needs therapeutic adjustment. The goal is to allow the child to restart his activities. A preventive sedation analgesia is necessary when a painful exam is to be performed, either for diagnosis or therapeutic purpose. For this goal ideal analgesics, either for monotherapy or associated, are easily and painlessly administered. They have rapid onset of action, brief half-life, predictable, effective analgesic properties without side effects and they are quickly reversible. These drugs do not exist and every sedation procedure has a risk of hypoxemia. With the human and equipment's investment an emergency department should be able to ensure that procedures are performed in children under sedation with a standard of safety that is similar to general anaesthesia. The main drawback in a well-organised system should be a significant children's rate for which general anaesthesia is preferred.
The methanolic extract of the stem bark of Parinari polyandra (family Rosaceae) was investigated for possible anti-nociceptive and anti-inflammatory effects in mice and rats. Three models were used to study the extracts effects on nociception which were the acetic acid-induced abdominal constriction test, hot-plate method (both in mice) and the formalin test in rats. The anti-inflammatory effects were investigated employing the albumin-induced hind-paw oedema in rats. Results of the study revealed the extract to have significant (P<0.05) anti-nociceptive effect at a dose of 200 mg/kg p.o. in mice and rats in all the models for anti-nociception while 100 mg/kg p.o. showed significant (P<0.05) effect in the acetic acid-induced abdominal constriction test and in phase I of the formalin test. The extract also exhibited anti-inflammatory effects which were found to be significant (P<0.05) at 200 mg/kg p.o. in the rats tested. Preliminary phytochemical screening of the extract showed the presence of flavonoids, tannins, and saponin glycoside. The results suggest the extract contains pharmacologically active principles. The result is in agreement with the local application of the plant in painful and inflammatory conditions.