Abstract:Clonidine is a centrally acting antihypertensive drug. Hypotensive effect of clonidine is mediated mainly by central a2-adrenoceptors and/or imidazoline receptors located in a complex network of the brainstem. Unfortunately, clonidine produces side effects such as sedation, mouth dry, and depression. Moxonidine and rilmenidine, compounds of the second generation of imidazoline drugs, with fewer side effects, display a higher affinity for the imidazoline receptors compared with a2-adrenoceptors. The antihyperte… Show more
“…Decarboxylation of L-arginine produces AGM, a cationic amine with potent biological activity. AGM exhibits a strong affinity for imidazoline and two adrenergic receptors and is present in numerous mammalian tissues [20]. The highest concentrations of AGM are found in the stomach, aorta, and small intestine, while lower concentrations are found in the spleen, adrenal gland, skeletal muscle, and brain [21].…”
Chronic inflammation and oxidative stress can contribute to the development of cardiovascular diseases. Isoproterenol (ISO), a synthetic catecholamine, is used to study the effects of drugs on cardiotoxicity. Agmatine (AGM) is a type of biogenic amine produced through the decarboxylation of arginine. The purpose of the current study was to evaluate the effects of AGM against ISO-induced cardiotoxicity due to the described roles of AGM in cardiovascular disease. Four groups of thirty-two Wistar Albino rats were divided equally as control, ISO, AGM+ISO, and ISO+AGM. ISO was administered intraperitoneally (i.p.) twice at a dose of 150 mg/kg, at 24-hour intervals. Prior to and after ISO injection, 20 mg/kg of AGM was injected i.p. Hemodynamic measurements and serum and tissue biochemical analyses were evaluated at the end of the experiment. The levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) in the tissue were measured. In the ISO group, levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were increased significantly (p<0.05). Co-administration of ISO and AGM significantly reduced CK and LDH levels (p<0.05). MDA levels increased in the ISO-treated group but decreased in the AGM-treated groups (p<0.05). Notably, there was a reduction in the CAT level in the ISO treatment group (p<0.05). CAT was found to be significantly increased (p<0.05) in the groups that received AGM compared to the ISO group. AGM+ISO group had a reduced density of degenerated cardiomyocytes and granulation tissue compared to the ISO group (p<0.05). Although granulation tissue demonstrated a significant reduction in the ISO+AGM group in comparison to the ISO group (p<0.05). In this study, the results indicate that AGM treatment can potentially inhibit ISO-induced myocardial injury and vascular dysfunction by preserving vascular integrity. Notably, the protective effects of AGM on cardiac damage appear to outweigh its therapeutic benefits, as shown by histopathological analysis
“…Decarboxylation of L-arginine produces AGM, a cationic amine with potent biological activity. AGM exhibits a strong affinity for imidazoline and two adrenergic receptors and is present in numerous mammalian tissues [20]. The highest concentrations of AGM are found in the stomach, aorta, and small intestine, while lower concentrations are found in the spleen, adrenal gland, skeletal muscle, and brain [21].…”
Chronic inflammation and oxidative stress can contribute to the development of cardiovascular diseases. Isoproterenol (ISO), a synthetic catecholamine, is used to study the effects of drugs on cardiotoxicity. Agmatine (AGM) is a type of biogenic amine produced through the decarboxylation of arginine. The purpose of the current study was to evaluate the effects of AGM against ISO-induced cardiotoxicity due to the described roles of AGM in cardiovascular disease. Four groups of thirty-two Wistar Albino rats were divided equally as control, ISO, AGM+ISO, and ISO+AGM. ISO was administered intraperitoneally (i.p.) twice at a dose of 150 mg/kg, at 24-hour intervals. Prior to and after ISO injection, 20 mg/kg of AGM was injected i.p. Hemodynamic measurements and serum and tissue biochemical analyses were evaluated at the end of the experiment. The levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) in the tissue were measured. In the ISO group, levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were increased significantly (p<0.05). Co-administration of ISO and AGM significantly reduced CK and LDH levels (p<0.05). MDA levels increased in the ISO-treated group but decreased in the AGM-treated groups (p<0.05). Notably, there was a reduction in the CAT level in the ISO treatment group (p<0.05). CAT was found to be significantly increased (p<0.05) in the groups that received AGM compared to the ISO group. AGM+ISO group had a reduced density of degenerated cardiomyocytes and granulation tissue compared to the ISO group (p<0.05). Although granulation tissue demonstrated a significant reduction in the ISO+AGM group in comparison to the ISO group (p<0.05). In this study, the results indicate that AGM treatment can potentially inhibit ISO-induced myocardial injury and vascular dysfunction by preserving vascular integrity. Notably, the protective effects of AGM on cardiac damage appear to outweigh its therapeutic benefits, as shown by histopathological analysis
“…Particular attention should be paid to I 3 -imidazoline receptors (I 3 R), which are found in the pancreas and stimulated, leading to increased insulin production by beta-cells. 5 Figure 1 Synthesis of some benzimidazole derivatives (IVa-f). …”
Section: Introductionmentioning
confidence: 99%
“…Particular attention should be paid to I 3 -imidazoline receptors (I 3 R), which are found in the pancreas and stimulated, leading to increased insulin production by beta-cells. 5 I 1 Rs are associated with phosphatidylcholine hydrolysis, the formation of arachidonic acid and eicosanoids, and are actively associated with catecholamine synthesis. Some studies indicate that I1Rs belong to neurocytokine receptors and are similar in action to interleukins.…”
Introduction
The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats.
Methods
The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances.
Results & Discussion
The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.
“…Therefore, this receptor system has been suggested as a promising target for the management of chronic pain [18][19][20]. The I 2 -R is a member of a wider family of imidazoline receptors, also including I 1 -R and I 3 -R, which play important roles in central cardiovascular regulation and in insulin secretion, respectively [21,22]. In particular, I 1 -R is involved in the hypotensive activity of clonidine and related compounds supporting the idea that the I 1 -Rs are upstream from the α 2adrenergic receptors and work in tandem for its effect on blood pressure [23].…”
Anti-cancer therapy based on the repeated administration of oxaliplatin is limited by the development of a disabling neuropathic syndrome with detrimental effects on the patient's quality of life. The lack of effective pharmacological approaches calls for the identification of innovative therapeutic strategies based on new targets. We focused our attention on the imidazoline I 1 receptor (I 1 -R) and in particular on the selective I 1 -R agonist 2-(1-([1,1′-biphenyl]-2-yl)propan-2-yl)-4,5-dihydro-1H-imidazole) (carbophenyline). The purpose of this work was the preclinical evaluation of the efficacy of carbophenyline on oxaliplatininduced neuropathic pain in mice. Carbophenyline, acutely per os administered (0.1-10 mg kg −1 ), induced a dose-dependent anti-hyperalgesic effect that was completely blocked by the pre-treatment with the I 1 -R antagonist 3 or the I 1 /α 2 receptor antagonist efaroxan, confirming the I 1 -R-dependent mechanism. Conversely, pre-treatment with the I 2 -R antagonist BU224 did not block the anti-nociceptive effect evoked by carbophenyline. Repeated oral administrations of carbophenyline (1 mg kg −1 ) for 14 days, starting from the first day of oxaliplatin injection, counteracted the development of neuropathic pain in all behavioral tests (cold plate, Von Frey, and paw pressure tests) carried out 24 h after the last carbophenyline treatment on days 7 and 14. In the dorsal horn of the spinal cord, carbophenyline significantly decreased the oxaliplatin-induced astrocyte activation detected by immunofluorescence staining by the specific labelling with GFAP antibody. In conclusion, carbophenyline showed anti-neuropathic properties both after acute and chronic treatment with preventive effect against oxaliplatin-induced astrocyte activation in the spinal cord. Therefore, I 1 -R agonists emerge as a new class of candidates for the management of oxaliplatin-induced neuropathic pain.
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