HBK-14 and HBK-15 Do Not Influence Blood Pressure, Lipid Profile, Glucose Level, or Liver Enzymes Activity after Chronic Treatment in Rats

• Published in: PloS one Vol. 11; no. 10; p. e0165495
• Main Authors: Pytka, Karolina, Głuch-Lutwin, Monika, Knutelska, Joanna, Jakubczyk, Magdalena, Waszkielewicz, Anna, Kotańska, Magdalena
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-10-2016; Public Library of Science (PLoS)
• Subjects: Alanine; Alanine transaminase; Animal experimentation; Animals; Antidepressants; Antioxidants; Anxiety; Anxiolytics; Aspartate; Aspartate aminotransferase; Biology and Life Sciences; Blood; Blood Glucose - metabolism; Blood lipids; Blood pressure; Blood Pressure - drug effects; Blood pressure measurement; Cholesterol; Cholesterol tests; Cytotoxicity; Dehydrogenases; Diabetes; Disorders; Drug dosages; Enzymes; Experiments; Free radicals; Glucose; Guinea Pigs; Hep G2 Cells; High density lipoprotein; Histamine - pharmacology; Histamine H1 receptors; Humans; Hypoglycemia; Hypotension; Ileum; Ileum - drug effects; Ileum - physiology; Laboratory animals; Lipids; Lipids - blood; Lipoproteins; Liver; Liver - drug effects; Liver - enzymology; Liver diseases; Low density lipoprotein; Low density lipoproteins; Male; Measuring instruments; Medicine and Health Sciences; Mental depression; Muscle Contraction - drug effects; Older people; Organic chemistry; Pharmacy; Phenyl Ethers - pharmacology; Physical Sciences; Piperazine; Piperazines - pharmacology; Plasma; Pressure measurement; Properties (attributes); Protein thiols; Psychiatry; Rats; Receptors; Research and Analysis Methods; Rodents; Thiols; Time Factors; Toxicity; Triglycerides; Poland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0165495

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 α1-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)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, γ-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 H1 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.