ISSN:
1432-2072
Keywords:
LM 5008
;
Quipazine
;
Metachlorophenylpiperazine
;
d-Fenfluramine
;
Serotonin uptake
;
Serotonin release
;
Serotonin receptor
;
Anorexia
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 4-(3-Indolyl-2-ethyl)piperidine (LM 5008), 2-(1-piperazinyl) quinoline (quipazine), and metachlorophenylpiperazine (mCPP) were studied for their ability to affect serotonergic mechanisms in vitro. Their relative potency in inhibiting serotonin (5-HT) uptake in vivo and reducing food intake in rats was also examined. mCPP was very potent in displacing 3H-5-HT bound to brain membranes (IC50, 6.2×10-7 M), followed by quipazine, which showed an IC50 of 3.8×10-6 M. LM 5008 was the least effective with an IC50 of 3.6×10-5 M. mCPP and quipazine were less potent than d-fenfluramine in releasing 14C-5-HT from brain synaptosomes, while LM 5008 caused no significant effects at a concentration of 10-5 M. Conversely, both in vitro and in vivo studies on 5-HT uptake showed that LM 5008 was the most potent compound in inhibiting 5-HT uptake and mCPP the least potent. Since a 50% reduction of food intake was not reached even with a dose of LM 5008 27-times higher than the ED50 for inhibiting 5-HT uptake in vivo, it is suggested that even marked inhibition of 5-HT uptake at central synapses is not sufficient per se to trigger serotonin-dependent anorexia in the rat. Increased release and/or direct stimulation of post-synaptic receptors may be necessary to obtain this effect. This could be of interest for developing new agents which can cause anorexia by interacting with brain serotonin.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00426657
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