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Chemical Compound Review:

Tocris-0781 N-[4-[[5-[3-(2-aminoethyl)- 1H-indol-5-yl]...

Synonyms: CHEMBL39317, SureCN1321182, ANW-60396, BPBio1_000001, CTK8B8457, ...

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High impact information on L-694247

[35S]GTPgammaS binding was stimulated by the mixed 5-HT1A/5-HT(1B/D) agonist L694247 in brain structures enriched in 5-HT1A binding sites, i.e., hippocampus (+140 +/- 14%), dorsal raphe (+70 +/- 8%), lateral septum (+52 +/- 12%), cingulate (+36 +/- 8%), and entorhinal cortex (+34 +/- 5%) [1].
The relative order of efficacy for activation of GIRK current was 5-HT approximately F 13714 approximately L 694,247 approximately LY 228,729>flesinoxan approximately (+/-)8-OH-DPAT [2].
L 694247 caused virtually no stimulation in regions with 5-HT1B/1D receptors, such as substantia nigra, caudate nucleus and putamen [3].
[35S]GTPgammaS binding was stimulated by the mixed 5-HT1A/1B/1D agonist L 694247 (10 microm) in human brain regions enriched in 5-HT1A binding sites [e.g. hippocampus (132-137%), superficial layers of the neocortex (37-61%), and cingulate and entorhinal cortex (34 and 32%, respectively)] [3].
The L 694247-mediated [35S]GTPgammaS-binding responses in human and monkey brain sections were antagonized by the selective, silent 5-HT1A antagonist WAY 100635 (10 microm) [3].

Biological context of L-694247

In decerebrated, spinalized rabbits, the selective 5-HT1B/1D receptor agonists L-694,247 (cumulative doses of 2 - 243 nmol kg-1 i.v.) and L-741,604 (cumulative doses of 3 - 307 nmol kg-1 i.v.), each caused the sural-gastrocnemius reflex to increase to 140% of pre-drug levels, and arterial blood pressure to rise by about 10 mmHg [4].
In addition, intraventricular injections of L-694,247 did not modify water intake in normohydrated rats [5].
Serotonin- or L-694,247-induced increase in cell proliferation was inhibited by a selective 5-HT1B receptor antagonist, SB-224289 [6].

Anatomical context of L-694247

L694247 caused little or no stimulation of [35S]GTPgammaS binding in brain regions with high densities of 5-HT(1B/D) binding sites (e.g., substantia nigra, striatum, central gray, and dorsal subiculum) [1].
Effect of third ventricle administration of L-694,247, a selective 5-HT1D receptor agonist, on water intake in rats [5].
A recently identified endogenous tetrapeptide, 5-HT-moduline (Leu-Ser-Ala-Leu, LSAL), which specifically antagonizes 5-HT1B/1D receptor activity, was also shown to reverse the stimulating action of L-694,247 on T cell proliferation [6].

Associations of L-694247 with other chemical compounds

The effects of L-694,247 are due to a specific interaction with 5-HT1D receptors, because its inhibitory effect on water intake in dehydrated rats is blocked by the previous administration of a 5-HT1D antagonist, GR 127935 (5 micrograms/rat), directly into the third ventricle [5].

Gene context of L-694247

L-694,247: a potent 5-HT1D receptor agonist [7].
The 5-HT1B receptor agonist, L-694,247, caused a dose-dependent excitatory effect on most pallidal neurons tested [8].

References

Autoradiography of serotonin 5-HT1A receptor-activated G proteins in guinea pig brain sections by agonist-stimulated [35S]GTPgammaS binding. Dupuis, D.S., Palmier, C., Colpaert, F.C., Pauwels, P.J. J. Neurochem. (1998) [Pubmed]
Differential ion current activation by human 5-HT(1A) receptors in Xenopus oocytes: evidence for agonist-directed trafficking of receptor signalling. Heusler, P., Pauwels, P.J., Wurch, T., Newman-Tancredi, A., Tytgat, J., Colpaert, F.C., Cussac, D. Neuropharmacology (2005) [Pubmed]
Autoradiographic studies of 5-HT1A-receptor-stimulated [35S]GTPgammaS-binding responses in the human and monkey brain. Dupuis, D.S., Pauwels, P.J., Radu, D., Hall, H. Eur. J. Neurosci. (1999) [Pubmed]
On the role of 5-HT1B/1D receptors in modulating transmission in a spinal reflex pathway in the decerebrated rabbit. Ogilvie, J., Wigglesworth, M., Appleby, L., Kingston, T.O., Clarke, R.W. Br. J. Pharmacol. (1999) [Pubmed]
Effect of third ventricle administration of L-694,247, a selective 5-HT1D receptor agonist, on water intake in rats. De Castro-e-Silva, E., Sarmento, C., Nascimento, T.A., Luz, C.P., Soares, T., Marinho, A., Cunha, M., Bulcäo, C., De Oliveira, I.R., Fregoneze, J.B. Pharmacol. Biochem. Behav. (1997) [Pubmed]
The proliferation of human T lymphoblastic cells induced by 5-HT1B receptors activation is regulated by 5-HT-moduline. Sibella-Argüelles, C. C. R. Acad. Sci. III, Sci. Vie (2001) [Pubmed]
L-694,247: a potent 5-HT1D receptor agonist. Beer, M.S., Stanton, J.A., Bevan, Y., Heald, A., Reeve, A.J., Street, L.J., Matassa, V.G., Hargreaves, R.J., Middlemiss, D.N. Br. J. Pharmacol. (1993) [Pubmed]
In vivo effects of local activation and blockade of 5-HT1B receptors on globus pallidus neuronal spiking. Querejeta, E., Oviedo-Chávez, A., Araujo-Alvarez, J.M., Quiñones-Cárdenas, A.R., Delgado, A. Brain Res. (2005) [Pubmed]

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