S-phenylpiracetam, a Selective DAT Inhibitor, Reduces Body Weight Gain Without Influencing Locomotor Activity

Pharmacol Biochem Behav. 2017 Sep;160:21-29. doi: 10.1016/j.pbb.2017.07.009. Epub 2017 Jul 22.

Abstract

S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Glucose Tolerance Test
  • Insulin / blood
  • Locomotion / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Piracetam / analogs & derivatives
  • Piracetam / pharmacology
  • Rats
  • Rats, Wistar
  • Rats, Zucker
  • Weight Gain / drug effects*

Substances

  • Blood Glucose
  • Dopamine Plasma Membrane Transport Proteins
  • Insulin
  • S-phenylpiracetam
  • Piracetam