Pharmacol Rep
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Comparative Study
Partial lesion of the dopaminergic innervation of the ventral striatum induces "depressive-like" behavior of rats.
Depression is a frequent comorbid disorder in Parkinson's disease (PD) which may precede appearance of its motor symptoms by several years. Pathomechanisms underlying PD have been suggested to be responsible for the PD-related depression. The aim of the study was to examine the influence of a partial lesion of striatal dopaminergic terminals on the "depressive-like" behavior of rats in the forced swimming test (FS). 6-Hydroxydopamine (6-OHDA) was injected bilaterally into the ventro-lateral region of the caudate-putamen (CP) (3.75 μg/2.5 μl/side). ⋯ Levels of dopamine, DOPAC and HVA were decreased in the nucleus accumbens (NAC) 2 weeks after 6-OHDA but were not changed in the CP, frontal cortex (FCX) and substantia nigra (SN). No significant effect of 6-OHDA on tyrosine hydroxylase-immunoreactivity in the CP and NAC were found. The present study indicates that a relatively small lesion of dopaminergic terminals in the ventral striatum, which does not produce any motor disturbances, may induce "depressive-like" symptoms.
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The kynurenine aminotransferases (KATs) KAT I and KAT II are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant. KAT I and II have been found in avian, rodent, and human retina. Expression of KAT I in Müller cell endfeet and KAT II in retinal ganglion cells has been documented. ⋯ In DBA/2J mice, a model of ocular hypertension, an age-dependent decrease of retinal KYNA and KATs was found. In the corpora amylacea in the human retina intensive KAT I and II immunoreactivity was demonstrated. In summary, these findings point to the potential involvement of KYNA in the mechanisms of retinal aging and neurodegeneration.
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In clinical practice, using the lowest doses of drugs for anesthesia or analgesia is the main goal. Opioid combinations with local anesthetics can be preferable for achieving adequate anesthesia or analgesia. The primary purpose of this study was to examine possible thermal antinociceptive effects of the opioid -fentanyl and the amide local anesthetics levobupivacaine and lidocaine when locally administered alone or in combination. ⋯ However, in the presence of fentanyl, the effects of levobupivacaine and lidocaine were different. Although co-injection of levobupivacaine with fentanyl both enhanced and prolonged antinociceptive action, the lidocaine-fentanyl combination did not significantly change the paw withdrawal latency. These results suggest that intraplantar co-administration of fentanyl with levobupivacaine, but not lidocaine, may provide more effective antinociception without increasing the dose requirements.
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Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. ⋯ This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels.
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Nefopam is a centrally acting non-opioid analgesic with a mechanism of action that is not completely understood. Adverse effects associated with the therapeutic use and overdose of nefopam are mainly associated with the central nervous system, such as hallucinations, cerebral edema and convulsions. The aim of this study was to assess the effect of nefopam on the electrical threshold and its influence on the protective activity of antiepileptic drugs in the maximal electroshock test in mice. ⋯ At a subthreshold dose of 1 mg/kg, nefopam significantly enhanced the anticonvulsant activity of valproate against electroconvulsions. The protective activity of phenobarbital and phenytoin was significantly enhanced by co-administration of nefopam at the 5 mg/kg dose, but this same dose of nefopam failed to affect the protective activity of carbamazepine. In conclusion, nefopam exerts an anticonvulsive effect when given alone and significantly enhances the protective activity of certain antiepileptic agents against electroconvulsions induced in mice.