Regional pattern of binding and c-Fos induction by (R)- and (S)-citalopram in rat brain.
Citalopram is a racemic mixture of two stereoisomers, (R)- and (S)-citalopram. Both enantiomers were radiolabelled and used for in vitro receptor autoradiography in rat brain. High levels of specific [3H](S)-citalopram binding were observed in the amygdala complex, substantia nigra, superior colliculus and central grey. No specific binding of [3H](R)-citalopram was observed in any brain regions examined. S-citalopram induced a significant increase in c-Fos positive cells in central amygdala and in the bed nucleus of the stria terminalis (BST), compared to vehicle controls. A similar pattern of c-Fos activation was observed with (RS)-citalopram, sertraline and paroxetine, while (R)-citalopram did not increase c-Fos expression in these areas. The high affinity binding and apparent neuronal activation by (RS)-citalopram is thus confined to the (S)-enantiomer.
Thomsen
Christian
C
Cabral-da-SilvaMolecular Pharmacology, H Lundbeck A/S, Biological Research, Valby, Denmark. ctho@lundbeck.com
Helboe
Lone
L
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D016760:Proto-Oncogene Proteins c-fos; D015283:Citalopram