LP 44

Selective 5-HT7 receptor agonists LP 44 and LP 211 elicit an analgesic effect on formalin-induced orofacial pain in mice.[Pubmed:27383702]

J Appl Oral Sci. 2016 May-Jun;24(3):218-22.

OBJECTIVE: To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice. MATERIAL AND METHODS: Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 microl of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0-12 min) and the late phase (Phase II: 12-30 min). RESULTS: LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test. CONCLUSION: Our results suggest that 5-HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain.

The serotonin 5-HT7 receptor agonist LP-44 microinjected into the dorsal raphe nucleus suppresses REM sleep in the rat.[Pubmed:18466985]

Behav Brain Res. 2008 Aug 22;191(2):184-9.

The effects of LP-44, a selective 5-HT7 receptor agonist, and of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of LP-44 (1.25-5.0 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Similar effects were observed after the direct administration into the DRN of SB-269970 (0.5-1.0 mM). Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods. It is proposed that the suppression of REMS after microinjection of LP-44 into the DRN is related, at least in part, to the activation of GABAergic neurons in the DRN that contribute to long projections that reach, among others, the laterodorsal and pedunculopontine tegmental nuclei involved in the promotion of REMS.

Detection of Lead in the Carbon-rich, Very Metal-poor Star LP 625-44: A Strong Constraint on s-Process Nucleosynthesis at Low Metallicity.[Pubmed:10859127]

Astrophys J. 2000 Jun 20;536(2):L97-L100.

We report the detection of the Pb i lambda4057.8 line in the very metal-poor (&sqbl0;Fe&solm0;H&sqbr0;=-2.7), carbon-rich star, LP 625-44. We determine the abundance of Pb (&sqbl0;Pb&solm0;Fe&sqbr0;=2.65) and 15 other neutron-capture elements. The abundance pattern between Ba and Pb agrees well with a scaled solar system s-process component, while the lighter elements (Sr-Zr) are less abundant than Ba. The enhancement of s-process elements is interpreted as a result of mass transfer in a binary system from a previous asymptotic giant branch (AGB) companion, an interpretation strongly supported by radial velocity variations of this system. The detection of Pb makes it possible, for the first time, to compare model predictions of s-process nucleosynthesis in AGB stars with observations of elements between Sr and Pb. The Pb abundance is significantly lower than the prediction of recent models (e.g., Gallino et al.), which succeeded in explaining the metallicity dependence of the abundance ratios of light s-elements (Sr-Zr) to heavy ones (Ba-Dy) found in previously observed s-process-enhanced stars. This suggests that one should either (1) reconsider the underlying assumptions concerning the (13)C-rich s-processing site ((13)C pocket) in the present models or (2) investigate alternative sites of s-process nucleosynthesis in very metal-poor AGB stars.

Structure-affinity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides, a new class of 5-hydroxytryptamine7 receptor agents.[Pubmed:15588097]

J Med Chem. 2004 Dec 16;47(26):6616-24.

A series of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides was prepared and their affinity for serotonin (5-hydroxytryptamine, 5-HT) 5-HT7, 5-HT(1A), and 5-HT(2A) receptors was measured by in vitro binding assays. In relation to 5-HT7 receptor affinity, receptor binding studies indicated that (i) the optimal alkyl chain length was five methylenes, (ii) an unsubstituted 1,2,3,4-tetrahydronaphthalenyl nucleus was preferred, and (iii) the substitution pattern of the aryl ring linked to the piperazine ring played a crucial role. Several compound with high affinity for 5-HT7 receptors were identified. Among them, 4-(2-methoxyphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (28), 4-(2-acetylphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (34), 4-(2-methylthiophenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanami de (44), 4-(2-hydroxyphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (46), and 4-(2-methylphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide (49) were assayed for the 5-HT7 receptor-mediated relaxation of substance P-induced guinea pig ileum contraction. Compounds 28, 44, and 49 behaved as full agonists and compound 34 as a partial agonist, whereas derivative 46 acted as an antagonist. Among the compounds presented here, it emerged that 44 was identified as a potent 5-HT7 receptor agonist (Ki = 0.22 nM, EC50 = 2.56 microM), endowed with selectivity over 5-HT(1A) and 5-HT(2A) receptors (200-fold and >1000-fold, respectively).