TY - JOUR
T1 - Differential behavioral syndrome evoked in the rats after multiple doses of SSRI fluoxetine with selective MAO inhibitors rasagiline or selegiline
AU - Speiser, Z.
AU - Fine, T.
AU - Litinetsky, L.
AU - Eliash, S.
AU - Blaugrund, E.
AU - Cohen, S.
PY - 2008/1
Y1 - 2008/1
N2 - This study investigated whether rasagiline and selegiline (MAO-B inhibitors) induce serotonin syndrome in fluoxetine-treated rats. Rats received rasagiline (0.1, 0.5, 2.0 mg/kg), or selegiline (0.8, 4.0, 16.0 mg/kg) (doses reflecting the clinical ratio of 1:8 base) in drinking water for 28 days. During the last 21 days, they received injections of fluoxetine 10 mg/kg (controls received water only, then saline injections; a fluoxetine only group received water only then fluoxetine). Serotonin syndrome was assessed using neurological severity score (NSS), food intake and weight gain. Mean NSS significantly increased, and weight and food consumption significantly decreased in rats receiving fluoxetine alone compared with controls. Selegiline 16 mg/kg but not rasagiline (regardless of dose) exacerbated these effects. We concluded that selegiline's amphetamine-like metabolites may increase synaptic cathecholamines and possibly serotonin, aggravating fluoxetine's effect. Rasagiline is devoid of this effect and may therefore be safer for use with serotonergic drugs in parkinsonian patients.
AB - This study investigated whether rasagiline and selegiline (MAO-B inhibitors) induce serotonin syndrome in fluoxetine-treated rats. Rats received rasagiline (0.1, 0.5, 2.0 mg/kg), or selegiline (0.8, 4.0, 16.0 mg/kg) (doses reflecting the clinical ratio of 1:8 base) in drinking water for 28 days. During the last 21 days, they received injections of fluoxetine 10 mg/kg (controls received water only, then saline injections; a fluoxetine only group received water only then fluoxetine). Serotonin syndrome was assessed using neurological severity score (NSS), food intake and weight gain. Mean NSS significantly increased, and weight and food consumption significantly decreased in rats receiving fluoxetine alone compared with controls. Selegiline 16 mg/kg but not rasagiline (regardless of dose) exacerbated these effects. We concluded that selegiline's amphetamine-like metabolites may increase synaptic cathecholamines and possibly serotonin, aggravating fluoxetine's effect. Rasagiline is devoid of this effect and may therefore be safer for use with serotonergic drugs in parkinsonian patients.
KW - Amphetamine-like activity
KW - Food consumption
KW - MAOIs
KW - NSS
KW - Rasagiline
KW - Selegiline
KW - Serotonin
KW - Serotonin syndrome
UR - http://www.scopus.com/inward/record.url?scp=37749047066&partnerID=8YFLogxK
U2 - 10.1007/s00702-007-0811-8
DO - 10.1007/s00702-007-0811-8
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AN - SCOPUS:37749047066
SN - 0300-9564
VL - 115
SP - 107
EP - 116
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 1
ER -