Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fenfluramine, m-chlorophenylpiperazine (m-CPP), 1-phenylpiperazine, and the buspirone metabolite, 1-(2-pyrimidyl)piperazine given intravenously to adult rhesus monkeys regularly elicited penile erections. In contrast, serotonin (5-HT) agonists with 5-HT1A site specificity (8-OH-DPAT, buspirone) as well as trazodone, ritanserin, and metergoline were no different from saline in producing penile erections. Fenfluramine's effects were blocked by the 5-HT2 antagonists, ritanserin and metergoline, while m-CPP's effects were not blocked by the peripheral 5-HT antagonist, xylamidine, indicating that tumescence can be elicited by serotonergic agents which act at non-5-HT1A sites in the central nervous system.
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PMID:Effects of fenfluramine, m-chlorophenylpiperazine, and other serotonin-related agonists and antagonists on penile erections in nonhuman primates. 317 81

The 5-HT1A receptor affinities and ionization constants of a set of 1-arylpiperazine (4) 1,2,3,4-tetrahydroisoquinoline (6), and -quinoline (7) containing N-(omega-arylalkyl) or N-(E)-cinnamyl substituents as well as two morpholine derivatives (8a, 8b) were determined. It was shown that some tetrahydroisoquinoline (6c, 6d) and morpholine (8a) derivatives were 5-HT1A ligands equipotentto 1-phenylpiperazine (4a) and 1,2,3,4,4a,5-hexahydropyrazino [1,2-a]indole (5). On the basis of molecular modelling studies it was also demonstrated that 6c, 6d and 8a mimicked very well the reference structures of 4a and its rigid analog 5. Another, more complex 1,2,3,4-tetrahydroisoquinoline derivative 3, which served as a model compound to confirm the previously reported 5-HT1A binding mode of derivatives 1a-d and 2, had the highest 5-HT1A affinity (Ki = 6.7 +/- 0.5 nM) of all the investigated compounds.
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PMID:Structure-activity relationship studies of CNS agents, Part 23: N-(3-phenylpropyl)- and N-[(E)-cinnamyl]-1,2,3,4-tetrahydroisoquinoline mimic 1-phenylpiperazine at 5-HT1A receptors. 749 65

Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] (10), its derivatives 11-15 and its analogs 16 and 17 were examined as ligands of serotonin 5-HT1A receptors. It was shown that compounds 12 and 14 had essentially the same 5-HT1A affinity as 1-phenylpiperazine and its rigid analog 7, whereas there were substantial differences in the steric arrangement of their crucial pharmacophores, i.e. aromatic and protonation centers. On the basis of the existing models and using the (+)-LSD structure as a template, a new, extended three-point topographic model of 5-HT1A receptors has been proposed.
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PMID:Structure-activity relationship studies of CNS agents--XVII. Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] as a probe defining the extended topographic model of 5-HT1A receptors. 764 2

A series of new 3-(omega-aminoalkyl)-5,5-disubstituted hydantoins, containing 1-phenylpiperazine, 1-(o-methoxyphenyl)piperazine or 1,2,3,4-tetrahydroisoquinoline fragments, were synthesized by standard alkylation procedures and their 5-HT1A and 5-HT2A receptor affinities were determined. It has been shown that the investigated derivatives are recognized by 5-HT1A and 5-HT2A receptors due to the presence of a 1-arylpiperazine fragment however, the terminal hydantoin moiety plays an important role in stabilization of the receptor-ligand complex. It has also been found that the two 1-phenylpiperazine derivatives 32 and 36 are new selective 5-HT2A receptor ligands (Ki = 34 and 37 nM, respectively), whereas the derivative of 1-(o-methoxyphenyl)piperazine (38) is a new, highly potent 5-HT1A receptor ligand (Ki = 0.51 nM) with a moderate affinity for 5-HT2A receptors (Ki = 213 nM).
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PMID:3-(omega-Aminoalkyl)-5,5-dialkyl(or spirocycloalkyl-1',5-)hydantoins as new 5-HT1A and 5-HT2A receptor ligands. 876 12

With an aim of creating new, mixed D-2/5-HT1A ligands, sixteen different compounds were synthesized. For this purpose 1-arylpiperazines attached through N-4 nitrogen to the dopaminergic pharmacophores of 2-(5-benzimidazole)-ethyl-, 2-(5-benztriazole)-ethyl-, 2-[5-(benzimidazole-2-thione]-ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]-ethyl-type were selected according to their structural diversity (phenyl, substituted phenyl, heteroaryl and naphthyl). All new compounds were checked for in vitro binding affinity at the dopamine (D-1 and D-2) and serotonin (5-HT1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampus were used as a source of dopamine and serotonin receptors, respectively, [3H]SCH 23390 (D-1 selective), [3H]spiperone (D-2 selective) and 8-OH-[3H]DPAT (5-HT1A selective) were employed as the radioligands. All compounds were inactive competitors of [3H]SCH 23390, 1c and 2b being inactive in the two other binding assays, as well. Derivatives of 1-(2-pyridyl)piperazine 1b and 2a and of 1-phenylpiperazine 1a expressed moderate to low affinity for both D-2 and 5-HT1A receptors, while 1-(2-pyridyl)-piperazines 3b and 4b and 4-(1-phenylethyl)-1-(1-naphthyl)-piperazine 10 were moderate [3H]spiperone, but potent 8-OH-[3H]DPAT competitors. Among them, derivatives of 1-(1-naphthyl)-piperazine 1e, 2d and 3e and of 1-(2,3-dimethylphenyl)-piperazine 1d, 2c and 3d were the strongest competitors at both D-2 and 5-HT1A receptors.
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PMID:Structure-affinity relationship studies on D-2/5-HT1A receptor ligands. 4-(2-Heteroarylethyl)-1-arylpiperazines. 910 40