The effects of tianeptine on wet-dog shakes, fore-paw treading and a flexor reflex in rats are consistent with enhancement of 5-hydroxytryptamine uptake.
Tianeptine is a novel antidepressant which uniquely facilitates 5-hydroxytryptamine (5-HT) uptake. When given in a dose of 10 mg/kg to rats pretreated with either carbidopa or phenelzine, it markedly reduced the frequency of wet-dog shakes, fore-paw treading, tremor and hind-limb abduction evoked by L-5-hydroxytryptophan (L-5-HTP) given 30 or 60 min later. This effect of tianeptine was opposite to that of paroxetine, a selective 5-HT uptake inhibitor, which greatly increased the 5-HTP-induced behavioural syndrome. In contrast, tianeptine did not affect behaviours elicited by the 5-HT receptor agonists, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), which are not substrates for the 5-HT uptake process. In spinal animals, tianeptine attenuated an ipsilateral flexor reflex, an effect opposite to that of citalopram, a selective 5-HT uptake inhibitor. These effects of tianeptine are consistent with its ability to increase 5-HT reuptake.
Department of Pharmacology, Nihon University School of Dentistry, Kanda-Surugadai, Tokyo, Japan.
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Koshikawa
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Mocaër
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JD
Stephenson
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002230:Carbidopa / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010624:Phenelzine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013841:Thiazepines / Q000494:pharmacology*
D000662:Amphetamines; D000929:Antidepressive Agents, Tricyclic; D008732:Methoxydimethyltryptamines; D012702:Serotonin Antagonists; D013841:Thiazepines; C050504:tianeptine; D012701:Serotonin; D002230:Carbidopa; D010624:Phenelzine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine