Hbk-14 And Hbk-15 Do Not Influence Blood Pressure, Lipid Profile, Glucose Level, Or Liver Enzymes Activity After Chronic Treatment In Rats

Older and even new antidepressants cause adverse effects, such as orthostatic hypotension, hyper-or hypoglycemia, liver injury or lipid disorders. In our previous experiments we showed significant antidepressant-and anxiolytic-like activities of dual 5-HT1A and 5-HT7 antagonists with alpha(1)-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxy)ethoxyethy1]-4-(2methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy) ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15). Here, we evaluated the influence of chronic administration of HBK-14 and HBK-15 on blood pressure (non-invasive blood pressure measurement system for rodents), lipid profile (total cholesterol, low density lipoproteins LDL, high density lipoproteins HDL, triglycerides), glucose level, and liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, y-glutamyl transferase). We determined potential antihistaminic (isolated guinea pig ileum) and antioxidant properties (ferric reducing ability of plasma FRAP, non-protein thiols NPSH, stable free radical diphenylpicrylhydrazyl DPPH) cytotoxicity. Our experiments revealed that HBK-14 and HBK-15 did not influence blood pressure, lipid profile, glucose level or liver enzymes activity in rats after 2-week treatment. We also showed that none of the compounds possessed antioxidant or cytotoxic properties at antidepressant-and anxiolytic-like doses. HBK-14 and HBK-15 very weakly blocked H-1 receptors in guinea pig ileum. Positive results of our preliminary experiments on the safety of HBK-14 and HBK-15 encourage further studies concerning their effectiveness in the treatment of depression and/or anxiety disorders.