Novel sigma (sigma) receptor agonists produce antidepressant-like effects in mice.
Many antidepressant drugs interact with sigma receptors and accumulating evidence suggests that these proteins mediate antidepressant-like effects in animals and humans. sigma Receptors are localized in brain regions affected in depression, further strengthening the hypothesis that they represent logical drug development targets. In this study, two novel sigma receptor agonists (UMB23, UMB82) were evaluated for antidepressant-like activity in mice. First, radioligand binding studies confirmed that the novel compounds had preferential affinity for sigma receptors. Second, the forced swim test, a well established animal model for screening potential antidepressant drugs, showed that both compounds dose-dependently reduced immobility time. The sigma receptor antagonist BD1047 attenuated the antidepressant-like effects of UMB23 and UMB82. Third, locomotor activity suggested that the effects of UMB23 and UMB82 in the forced swim test were not due to non-specific motor activating effects. Together, the data provide further evidence that sigma receptor agonists represent a possible new class of antidepressant medication.
Wang
Jiajia
J
Department of Pharmacology, University of Mississippi, University, MS 38677, USA.
Mack
Aisha L
AL
Coop
Andrew
A
Matsumoto
Rae R
RR
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005029:Ethylenediamines / Q000494:pharmacology / Q000627:therapeutic use; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000819:agonists* / Q000037:antagonists & inhibitors; D013550:Swimming
C526779:1-(3-phenylpropyl)piperidine; C526780:2-(3,4-dichlorophenyl)-N-ethyl-N-(2-piperidin-1-ylethyl)ethanamine; D000928:Antidepressive Agents; D005029:Ethylenediamines; D010880:Piperidines; D017480:Receptors, sigma; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin