title: 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: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Karolina
authors: http://orcid.org/0000-0001-7134-9515
authors: K
authors: Pytka
authors: Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Monika
authors: M
authors: Głuch-Lutwin
authors: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Joanna
authors: J
authors: Knutelska
authors: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Magdalena
authors: M
authors: Jakubczyk
authors: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Anna
authors: A
authors: Waszkielewicz
authors: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Magdalena
authors: M
authors: Kotańska
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D006168:Guinea Pigs; D056945:Hep G2 Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010647:Phenyl Ethers / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
chemical_list: D001786:Blood Glucose; C000620800:HBK-14; C000620801:HBK-15; D008055:Lipids; D010647:Phenyl Ethers; D010879:Piperazines; D000077489:Piperazine; D006632:Histamine