TY - JOUR
T1 - Attenuated Weight Gain with the Novel Analog of Olanzapine Linked to Sarcosinyl Moiety (PGW5) Compared to Olanzapine
AU - Taler, Michal
AU - Vered, Israel
AU - Globus, Rea
AU - Shbiro, Liat
AU - Weizman, Abraham
AU - Weller, Aron
AU - Gil-Ad, Irit
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Olanzapine-induced weight gain is associated with atherosclerosis, hypertension, dyslipidemia, and diabetes. We synthesized a novel antipsychotic drug (PGW5) possessing an olanzapine moiety linked to sarcosine, a glycine transporter 1 inhibitor. In this study, we compared the metabolic effects of PGW5 and olanzapine in a female rat model of weight gain. Female rats were treated daily with oral olanzapine (4 mg/kg), PGW5 (25 mg/kg), or vehicle for 16 days. Behavioral tests were conducted on days 12–14. Biochemical analyses were performed at the end of the treatment. A significant increase in body weight was observed in the olanzapine-treated group, while the PGW5 group did not differ from the controls. The open field test showed hypo-locomotion in the olanzapine-treated animals as compared to PGW5 and control groups. A significant increase in hypothalamic protein expression of the neuropeptide Y5 receptor and a decrease in pro-opiomelanocortin messenger ribonucleic acid (mRNA) levels were detected following PGW5 treatment, but not after olanzapine administration. PGW5 appears to possess minor metabolic effects compared with the parent compound olanzapine. The differential modulation of brain peptides associated with appetite regulation is possibly involved in the attenuation of metabolic effects by PGW5.
AB - Olanzapine-induced weight gain is associated with atherosclerosis, hypertension, dyslipidemia, and diabetes. We synthesized a novel antipsychotic drug (PGW5) possessing an olanzapine moiety linked to sarcosine, a glycine transporter 1 inhibitor. In this study, we compared the metabolic effects of PGW5 and olanzapine in a female rat model of weight gain. Female rats were treated daily with oral olanzapine (4 mg/kg), PGW5 (25 mg/kg), or vehicle for 16 days. Behavioral tests were conducted on days 12–14. Biochemical analyses were performed at the end of the treatment. A significant increase in body weight was observed in the olanzapine-treated group, while the PGW5 group did not differ from the controls. The open field test showed hypo-locomotion in the olanzapine-treated animals as compared to PGW5 and control groups. A significant increase in hypothalamic protein expression of the neuropeptide Y5 receptor and a decrease in pro-opiomelanocortin messenger ribonucleic acid (mRNA) levels were detected following PGW5 treatment, but not after olanzapine administration. PGW5 appears to possess minor metabolic effects compared with the parent compound olanzapine. The differential modulation of brain peptides associated with appetite regulation is possibly involved in the attenuation of metabolic effects by PGW5.
KW - Neuropeptide Y (NPY)
KW - Olanzapine
KW - PGW5
KW - Pro-opiomelanocortin (POMC)
KW - Weight gain
UR - http://www.scopus.com/inward/record.url?scp=84957432257&partnerID=8YFLogxK
U2 - 10.1007/s12031-015-0679-2
DO - 10.1007/s12031-015-0679-2
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C2 - 26572534
AN - SCOPUS:84957432257
SN - 0895-8696
VL - 58
SP - 66
EP - 73
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 1
ER -