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Effects of sigma agonist and antagonist drugs on food and/or water intake in rats
Author(s) -
Katz Norman L.,
Sobaski Nancy,
Sanchez Jenny,
Kremer Edna K.,
Lee Jamie K.,
Schlemmer R. Francis
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430190106
Subject(s) - agonist , antagonist , chemistry , medicine , endocrinology , sigma receptor , pharmacology , receptor
Abstract Drugs known to interact with sigma receptors were studied for their effects on food and/or water intake, since the putative sigma receptor agonist N‐allylnormetazocine (NANM) has been reported to both increase and decrease food intake under various conditions. Previous investigators have shown that each enantiomer of racemic NANM [(±)‐NANM] is pharmacologically active. (+)‐NANM appears to interact preferentially with sigma receptors, and (−)‐NANM with both mu and kappa opiate receptor sites. In the present study, the effects of subcutaneously administered (±)‐NANM, (+)‐NANM, and (−)‐NANM on food intake in 20 hr food‐deprived male rats were examined. (±)‐NANM and (−)‐NANM decreased food intake stimulated by food deprivation, while (+)‐NANM exhibited no significant effect. Similarly, both (±)‐NANM and (−)‐NANM decreased water intake in 24 hr water‐deprived rats. (+)‐NANM decreased water intake in doses which may have caused disorientation. Locomotor activity was stimulated by intraperitoneal injection of 10 mg/kg of (+)‐NANM but not by the same dose of (−)‐NANM. The effects of (+)‐NANM and (−)‐NANM on food and water intake paralleled those of narcotic antagonists and did not seem related to an interaction with sigma receptors. (±)‐BMY14802 is a sigma receptor antagonist with potential antipsychotic properties. When administered to female rats by daily injection for 28 days, it did not affect weight gain except at the highest dose, 30 mg/kg. Weight gain of animals given a 30 mg/kg dose was significantly greater compared to controls. However, rats treated orally with a similar dose of (±)‐BMY14802 incorporated into the diet daily for 8 weeks did not exhibit significant weight gain compared to controls. The data argue against a significant role for sigma receptors in mediating ingestive behavior. Should sigma antagonist drugs reach the market, they may be less likely to cause weight gain than most classical antipsychotics.