5-HT(1A) receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential
by
Koek W, Vacher B, Cosi C, Assie M,
Patoiseau J, Pauwels PJ, Colpaert FC.
Centre de Recherche Pierre Fabre,
17 Ave. Jean Moulin, 81106 Cedex, Castres, France
Eur J Pharmacol 2001 May 25; 420(2-3):103-112

ABSTRACT

To examine further the hypothesis that the magnitude of the intrinsic activity of agonists at 5-HT(1A) receptors determines the magnitude of their psychotropic activity, we studied the relationship between the maximal receptor activation produced by various 5-HT(1A) receptor ligands and their antidepressant-like effects (i.e., decreased immobility in the forced swimming test in rats). Using three different in vitro assays suitable to measure differences among high, intermediate, and low efficacy 5-HT(1A) receptor agonists, ligands were identified with intrinsic activities ranging from low-negative (i.e., the inverse agonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide (WAY 100635)) to high-positive (i.e., 3-chloro-4-fluorophenyl-(4-fluoro-4-{[(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl-methanone (F 13714)). In addition, novel compounds with intermediate intrinsic activity, like buspirone, but with high selectivity for 5-HT(1A) receptors, unlike buspirone, were identified. The maximal effects of the 5-HT(1A) receptor ligands in the forced swimming test correlated positively (r(S)=0.91, P<0.005) with the rank order of their intrinsic activity at 5-HT(1A) receptors. This relationship constitutes evidence that the magnitude of the psychotropic activity of 5-HT(1A) receptor ligands is a positive function of their intrinsic activity at the receptor, and suggests that F 13714, which had maximal effects in the forced swimming test significantly larger than any of the other compounds examined here, did so because of its higher intrinsic activity at 5-HT(1A) receptors.

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5-HT2c/5-HT2b
5-HT1a v 5-HT1b
MDMA and 5-HT1a
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5-HT1a and F11440
Genomics and mood disorders
5-HT1a and atypical neuroleptics
5-HT1a agonists as antidepressants

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