Polish journal of pharmacology
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Comparative Study Clinical Trial
Influence of doxepin used in preemptive analgesia on the nociception in the perioperative period. Experimental and clinical study.
The aim of the present research was to assess in experimental and clinical study the influence of doxepin administered intraperitoneally (ip) as preemptive analgesia on the nociception in the perioperative period. The pain thresholds for mechanical stimuli were measured in rats. The objective of clinical investigation was to assess the influence of preemptive administration of doxepin on postoperative pain intensity, analgesic requirement in the early postoperative period as well as an assessment of the quality of postoperative analgesia by the patient. ⋯ Injection of 10 mg/kg of doxepin 30 min before formalin further enhanced the response after morphine administration. The results of the clinical study demonstrated that the patients who were administered doxepin preemptively showed significantly lower pethidine requirement in order to achieve a similar level of postoperative analgesia. The results of the research under discussion confirm the theoretical assumptions that there is a possibility to modify the nociception process in the perioperative period through preemptive analgesia using a drug that modifies the activity of the descending antinociceptive system.
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Emergent or elective surgical procedures under general anesthesia may be required during pregnancy for some patients. For this reason, effects of anesthetics on uterine contractions are important. General anesthesia is not limited to the administration of inhalation agents, since induction and maintenance of anesthesia usually involve intravenous administration of different anesthetic agents. ⋯ In our study, we examined the effects of ketamine, propofol and midazolam on contractions of isolated pregnant rat myometrium. We observed that exposure to propofol, ketamine and midazolam at the concentrations of 10(-5)-10(-4) M decreased spontaneous contractile activity in myometrial strips isolated from pregnant rats. There was statistically significant difference between the control and all strips exposed to propofol, ketamine and midazolam in the contraction amplitude and integrated area under the contraction curve.
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Comparative Study
Strychnine-insensitive glycine/NMDA sites are altered in two stress models of depression.
Chronic severe stress (CSS) and chronic mild stress (CMS) affect the properties of [3H]5,7-dichlorokynurenic acid (5,7-DCKA) binding to strychnine-insensitive glycine/NMDA sites in the rat cerebral cortex. Specifically, CSS decreases, while CMS increases, the potency of glycine to displace [3H]5,7-DCKA binding to glycine/NMDA sites. Moreover, in both models, a reduction of the specific [3H]5,7-DCKA binding was observed. The present results demonstrate the involvement of the cortical NMDA receptor complex in the animal models of depression.
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Polarized liver cells, hepatocytes, are involved in carbohydrate, protein and fat metabolism, breakdown of hemoglobin and production of bile. They are also involved in overall detoxification processes in an organism associated with the transport of bile salts, cholesterol, phospholipids, endo- and xenobiotics, end-products of cellular metabolism and ions through the canalicular region of the hepatocyte plasma membrane. ⋯ Canalicular transport includes the following transport systems: a specific canalicular transporter for bile salts, a multidrug resistance 2 P-glycoprotein (MDR2) participating in the transport of lipids, a multidrug resistance 3 P-glycoprotein (MDR3) responsible for the transport of organic cations and the multispecific organic anion transporter (cMOAT) involved in the transport of non-bile acid organic anions. The cMOAT transport system is discussed in this detailed review.
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Review Comparative Study
Potential role of 5-HT2 and D2 receptor interaction in the atypical antipsychotic action of the novel succimide derivative, perospirone.
The pharmacological profile of the novel serotonin-dopamine antagonists (SDA)-type antipsychotic, perospirone, was compared with other SDA and typical antipsychotics, and a potential role of 5-HT2 and D2 receptor interaction in the atypical antipsychotic property of SDA was discussed based on the findings with selective 5-HT2 antagonists. Our study revealed that perospirone, like other SDA, differed from the typical antipsychotics by exhibiting 1) putative anxiolytic and/or antidepressant actions in some animal models (e.g., conditioned fear stress-induced freezing model and rat social interaction), 2) reduced extrapyramidal side effects (EPS) liability (catalepsy and bradykinesia induction), 3) weaker blocking actions at striatal D2 receptors as revealed by c-fos expression and dopamine turnover and 4) lower propensity to induce supersensitivity of dopamine receptors after repeated treatments (e.g., dopamine agonist-induced stereotyped behavior and vacuous chewing movement). ⋯ In addition, combined treatments of 5-HT2 antagonists with typical antipsychotic could attenuate EPS induction and striatal c-fos expression associated with D2 receptor blockade, and could prevent the sensitization of D1 receptor function after repeated treatments. These findings suggest that the blockage of 5-HT2 receptors contributes to the broad efficacy profile of SDA (i.e., antipsychotic and mood stabilizing actions) and may counteract the D2 (and/or D1) blocking activities of antipsychotics in the striatum to reduce EPS.