Interactions of selective serotonin reuptake inhibitors with subtypes of sigma receptors in rat brain.
The interactions of selective serotonin reuptake inhibitors and tricyclic antidepressants with subtypes of sigma receptors were investigated. The rank order of affinity (Ki values) from competition experiments of [3H](+)-pentazocine binding to sigma 1 sites was: fluvoxamine > sertraline > S(+)-fluoxetine > (+/-)-fluoxetine > citalopram > imipramine > paroxetine > desipramine > R(-)-fluoxetine > (+/-)-norfluoxetine. The Ki values of all drugs for sigma 2 sites were more than 1000 nM. Furthermore, all drugs were more potent at sigma 1 sites than at sigma 2 sites. These findings suggest that sigma receptors (sigma 1 site) may play, in some way, a role in the actions of selective serotonin reuptake inhibitors.
Narita
N
N
Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
Hashimoto
K
K
Tomitaka
S
S
Minabe
Y
Y
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D003891:Desipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; D005473:Fluoxetine; D007099:Imipramine; D017465:Receptors, Opioid, delta; D017367:Selective Serotonin Reuptake Inhibitors; C036139:norfluoxetine