Antinociceptive and anxiolytic-like effects of some compounds carrying benzothiazole ring

Bu çalışmanın amacı benzotiyazol halkası taşıyan bazı bileşiklerin antinosiseptif ve anksiyolitik-benzeri etkilerinin incelenmesidir. 40 mg/kg dozda uygulanan test bileşiklerinin antinosiseptif etkileri kuyruk sıkıştırma, sıcak plaka ve asetik asid ile indüklenen kıvranma testleri ile araştırılmıştır. Bileşiklerin anksiyolitik-benzeri etkilerini incelemek için delikli tahta ve yükseltilmiş artı labirent testleri gerçekleştirilmiştir. Farelerin motor koordinasyonlarını değerlendirmek üzere Rota-rod cihazı kullanılmıştır. Deneyler sonucunda 3f, 3g ve 3h kodlu bileşiklerin kuyruk sıkıştırma ve sıcak plaka testlerinde hayvanların reaksiyon sürelerini artırdığı ve 3e kodlu bileşiğin ise asetik asid ile indüklenen kıvranma testinde farelerin kıvranma sayılarını azalttığı belirlenmiştir. Diğer yandan, 3f, 3g ve 3h kodlu bileşikler delikli tahta testinde farelerin ilk baş daldırma sürelerini kısaltırken toplam baş daldırma sayılarını artırmıştır. Yükseltilmiş artı labirent testinde ise aynı türevlerin farelerin açık kola giriş sayılarının ve açık kolda kalma sürelerinin yüzdelerini artırdığı ortaya konulmuştur. Rota-rod testlerinde test bileşikleri farelerin dönen milden düşme sürelerini değiştirmemiştir. Tüm bu bulgular, 3f, 3g ve 3h kodlu bileşiklerin santral antinosiseptif ve anksiyolitik-benzeri etki gösterdiklerine; 3e kodlu bileşiğin ise periferal antinosiseptif etki gösterdiğine işaret etmektedir.The aim of this study was to examine the antinociceptive and anxiolytic-like effects of some compounds carrying benzothiazole ring. The antinociceptive effects of test compounds, administrated at a dose of 40 mg/kg, were investigated by tail clip, hot plate and acetic acid-induced writhing tests. Hole board and elevated plus maze tests were performed to evaluate the anxiolytic-like effects of the compounds. Rota-rod device was used to assess the motor coordinations of mice. As a result of the experiments, it was determined that compounds 3f, 3g and 3h increased the reaction times of animals in the tail clip and hot plate tests, and compound 3e reduced the writhing number of mice in the acetic acid-induced writhing test. On the other hand, in the hole board test, compounds 3f, 3g and 3h reduced the first head-dipping latencies of mice while increasing the total number of head-dips. In the elevated plus maze test, it has been shown that the same derivatives increase the percentages of open arm entries and time spent in the open arms. In the Rota-rod tests, test compounds did not change the falling time of mice from the rotating mill. All these findings point out that compounds 3f, 3g and 3h exhibit central antinociceptive and anxiolytic-like effects and compound 3e shows a peripheral antinociceptive effect

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1–3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials

Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall–Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α2- and β2-adrenoceptors, D2/3 dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain

Antihyperalgesic Activity of Atomoxetine on Diabetes-Induced Neuropathic Pain: Contribution of Noradrenergic and Dopaminergic Systems

Atomoxetine is a selective noradrenaline reuptake inhibitor drug. Based on the knowledge that agents increasing monoamine levels in the central nervous system have therapeutic potential for neuropathic pain, it is planned to investigate the possible efficacy of atomoxetine on diabetes-induced hyperalgesia, in this study. Randall-Selitto (mechanical noxious stimuli) and Hargreaves (thermal noxious stimuli) tests were used to evaluate nociceptive perception of rats. Obtained data indicated that streptozotocin-induced diabetes causes significant decreases in the paw withdrawal threshold and paw withdrawal latency values of the animals, respectively. However, atomoxetine administered at 3 mg/kg/day for 7 and 14 days improved these diabetes-induced hyperalgesia responses. Furthermore, antihyperalgesic activity was antagonized with α-methyl-para-tyrosine methyl ester, phentolamine, propranolol, and sulpiride pre-treatments. The same effect was not reversed, however, by SCH 23390. These findings demonstrated, for the first time, that atomoxetine possesses significant antihyperalgesic activity on diabetes-induced neuropathic pain and this effect seems to be mediated by α- and β-adrenergic and D2/D3 dopaminergic receptors. Results of this present study seem to offer a new indication for an old drug; atomoxetine, but these preclinical data should first be confirmed with further well-designed clinical trials