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

Abstract

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.

• Authors: Karolina Pytka, Monika Głuch-Lutwin, Joanna Knutelska, Magdalena Jakubczyk, Anna Waszkielewicz, Magdalena Kotańska
• Journal: PloS one (PLoS One) Vol. 11 Issue 10 Pg. e0165495 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27788267 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• HBK-14
• HBK-15
• Lipids
• Phenyl Ethers
• Piperazines
• Piperazine
• Histamine

Topics

• Animals
• Blood Glucose (metabolism)
• Blood Pressure (drug effects)
• Guinea Pigs
• Hep G2 Cells
• Histamine (pharmacology)
• Humans
• Ileum (drug effects, physiology)
• Lipids (blood)
• Liver (drug effects, enzymology)
• Male
• Muscle Contraction (drug effects)
• Phenyl Ethers (pharmacology)
• Piperazine
• Piperazines (pharmacology)
• Rats
• Time Factors