Effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine on 5-HTP-induced behaviour.
The effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine (5, 10, 20 mg/kg, i.p.) on wet dog shakes (WDS) and faecal pellet production induced by concurrently administered 5-hydroxytryptophan (5-HTP, 100 mg/kg, i.p.) given 30 min after carbidopa (25 mg/kg, i.p.) were investigated in rats. WDS scores peaked approximately 1 hr after giving 5-HTP and gradually declined over the next 2 hr. (-)-Tianeptine dose-dependently and significantly inhibited WDS. Inhibition became less marked with time after administration, but remained significant over the 3 hr period after the 10 and 20 mg/kg doses and during the first 40 min after the 5 mg/kg dose. (+)-Tianeptine caused slight inhibition without dose-dependence and slightly increased net inhibition when added to the (-) isomer (10 mg/kg). The induction of faecal pellet production by 5-HTP was significantly and dose-dependently inhibited by (-)-tianeptine. The (+) isomer neither altered this effect of 5-HTP nor its inhibition by (-)-tianeptine. Results show that inhibition of 5-HTP-induced WDS and faecal pellet formation by tianeptine was almost completely dependent on the (-) isomer.
Oluyomi
A O
AO
Department of Neurochemistry, Institute of Neurology, London, U.K.
Datla
K P
KP
Curzon
G
G
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013841:Thiazepines / Q000737:chemistry / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine; D006916:5-Hydroxytryptophan