Pharmacology
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Comparative Study
Characterization of two models of drug-induced constipation in mice and evaluation of mustard oil in these models.
Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. ⋯ Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.
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Numerous agents have been demonstrated to potentiate morphine analgesia, including clonidine (alpha(2)-adrenergic and I(1)-imidazoline receptor agonist) and BMS182874 (endothelin-A, ET(A,) receptor antagonist). ET has been shown to affect pharmacological actions of clonidine. The present study was conducted to determine whether alpha(2)-adrenergic and/or I(1)-imidazoline receptors are involved in the augmentation of morphine and oxycodone analgesia by clonidine and BMS182874. ⋯ This is the first report showing that clonidine and BMS182874 augment oxycodone analgesia. Results suggest that alpha(2)-adrenergic receptors are involved in clonidine-induced, but not in the BMS182874-induced, potentiation of the analgesic effects of morphine or oxycodone, and that I(1)-imidazoline receptors are involved in the potentiation of oxycodone analgesia, but not morphine analgesia, by clonidine and BMS182874.
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In order to further elucidate the mechanism(s) of action of analgesic and antihyperalgesic nefopam, its interactions with the transient receptor potential vanilloid subtype 1 (TRPV1) were investigated. In sensory neurons of rat embryos, dorsal root ganglion (DRG) in culture, nefopam (3-30 mumol/l) and capsazepine (TRPV1 antagonist, 10 mumol/l) prevented intracellular calcium elevation and calcitonin gene-related peptide release induced by vanilloid agonist capsaicin. ⋯ In vivo, nefopam (0.5 and 2 mg/kg, i.v.) and capsazepine (40 mg/kg, i.p.) reduced the licking response due to intraplantar injection of capsaicin in mice. These findings suggest that nefopam exerts its analgesic and antihyperalgesic effects through multiple mechanisms including blockade of TRPV1 in addition to voltage-dependent calcium channels in the DRG.
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DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a hypersensitivity reaction with skin rashes, eosinophilia, fever, lymph node enlargement and internal organ involvement. ⋯ Vancomycin can be a cause of DRESS syndrome. A high index of suspicion is warranted in order not to miss this potentially lethal disease.
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There is evidence that both cholinergic and GABAergic systems are involved in the neurobiology of anxiety. In the present study, we investigated the effects and interaction of nicotinic and GABAergic systems in the central amygdala of rats, using the elevated plus maze test of anxiety. Bilateral administration of nicotine (1 and 2 microg/rat; 1 microl/rat; 0.5 microl/rat in each side) into the central amygdala (intra-CeA) induced an anxiogenic-like effect, shown by specific decreases in the percentage of open-arm time (%OAT) and percentage of open arm entries (%OAE). ⋯ Nicotine in a subeffective dose (0.25 microg/rat) when co-administered with muscimol did not significantly increase the anxiety behaviour. An effective dose of nicotine (2 microg/rat) in combination with bicuculline (0.25, 0.5 and 1 microg/rat) had no interaction on %OAT, %OAE and locomotor activity. It can be concluded that in the central amygdala, the GABAergic system is not involved in the anxiogenic response to nicotine.