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)

1. Radioligand binding with [125I]-cyanopindolol in the presence of isoproterenol was used to define the distribution of 5-HT1B receptors in the superior colliculus (SC) of adult hamsters. There was a high density of these receptors in the stratum griseum superficiale (SGS), and they were much less dense in other SC laminae. Enucleation of one eye produced a marked reduction in the density of these receptors in the contralateral SGS, suggesting that they are located primarily on retinotectal axon terminals. 2. Intracellular recording techniques were used to evaluate the effects of serotonin (5-HT) on the excitatory postsynaptic potentials (EPSPs) evoked in SC cells of adult hamsters by stimulation of the optic tract (OT) in vitro. Application of 5-HT produced a reduction of > or = 50% in OT-evoked EPSPs in 79% of the 67 cells tested. The average EPSP amplitude was 7.8 +/- 2.1 (SD) mV under control conditions and 2.7 +/- 1.9 mV in the presence of 5-HT (P < 0.01). For most of these neurons, application of 5-HT had little effect on their membrane potential or input resistance. The average percent change in membrane potential for cells tested with 5-HT was 0.5 +/- 6.0% and the average percent change in input resistance was 0.6 +/- 22.9%. 3. For four of six cells tested, application of 5-HT had no significant effects on the responses evoked by application of glutamate, either under normal bathing conditions or when the medium included low Ca2+ and high Mg2+. 4. Pharmacologic experiments indicated that the effects of 5-HT on retinotectal transmission were mimicked by the 5-HT1B agonists 1-[3-(trifluoromethyl)phenyl]-piperazine and 7-trifluoromethyl-4(4-methyl-1-piperazinyl) [1,2-a]-quinoxaline maleate and antagonized by the 5-HT1A/1B antagonists (-)-pindolol and methiothepin. The effects of 5-HT on the OT-evoked EPSP were not antagonized by either spiperone, ketanserin, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine HBr, or [1-H-3 alpha-5 alpha-tropan-3-yl]-3,5-dichlorobenzoate. 5. Both the anatomic and physiological results are consistent with the conclusion that 5-HT presynaptically inhibits retinotectal transmission and that this effect is mediated by the 5-HT1B receptor.
 ...
PMID:Modulation of retinotectal transmission by presynaptic 5-HT1B receptors in the superior colliculus of the adult hamster. 796 14

The effect of serotonin [5-hydroxytryptamine (5-HT)] on pial venous tone of the pig was examined using in vitro tissue bath techniques. Isolated pial venous rings exhibited spontaneous rhythmic contractions (SRC) on mechanical stretching and/or applications of several vasoactive substances, including norepinephrine. On the other hand, KCl induced sustained active muscle tone (SAT) without SRC. The SRC induced by mechanical stretching were not affected by tetrodotoxin, nitro-L-arginine, alpha- and beta-adrenergic, histaminergic, and muscarinic receptor antagonists, indicating that the SRC in porcine pial veins are of myogenic origin. The SRC induced by stretching or applications of vasoactive substances and SAT induced by KCl were inhibited by 5-HT in a concentration-dependent manner. The inhibition was prevented by methysergide and methiothepin but not by ketanserin, propranolol, 3 alpha-tropanyl-1H-indole-3-carboxylic acid ester, hemoglobin, or nitro-L-arginine. The SRC and SAT were inhibited by 5-carboxamidotryptamine (5-CT), 8-hydroxy-2-di-N-propylaminotetralin HBr (8-OHDPAT), 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP), and 5-methoxytryptamine (5-MT), but not by sumatriptan, alpha-methylserotonin, or 2-methylserotonin. On the other hand, 5-CT, 8-OHDPAT, TFMPP, 5-MT, and sumatriptan constricted the porcine pial arteries exclusively. In 15% of pial venous preparations examined, 5-HT at low concentrations induced ketanserin-sensitive constrictions. These results indicate that the porcine pial venous smooth muscle contains multiple subtypes of 5-HT receptors. The 5-HT inhibition of SRC and SAT is predominant and is mediated by 5-HT1-like receptors, which, however, do not seem to correspond to 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT1E, or 5-HT1F receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonin relaxes porcine pial veins. 816 Aug 3

To study interactions between DA and 5-HT neurochemical systems in the DA D1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a variety of 5-HT receptor agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form) 1 h before 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). When these rats were studied as adults it was determined that the striatal content of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by 98%, while the striatal content of 5-HT was elevated by 75%. The Bmax and Kd for [3H]SCH 23390 and [3H]spiperone binding to striatal homogenates was unaltered in the lesioned rats. However, oral activity responses to a D1 agonist (SKF 38393), D2 antagonist (spiperone) and 5-HT1C agonist [1-(3-chlorophenyl)piperazine] were enhanced several fold in the lesioned rats. Several other agonists and antagonists that act at 5-HT1A, 5-HT1B, 5-HT2 and 5-HT3 receptors did not produce an altered response in the lesioned rats, nor were these substances effective in attenuating m-CPP-enhanced oral activity responses. The DA D1 receptor antagonist, SCH 23390 HCl (0.30 mg/kg i.p.), did not attenuate the response to m-CPP 2HCl (1.0 mg/kg i.p.). However, the 5-HT receptor antagonist, mianserin HCl (1.0 mg/kg s.c.) did effectively attenuate the oral activity response to SKF 38393 HCl (1.0 mg/kg i.p.). These findings indicate that there is supersensitization of both DA D1 and 5-HT1C receptors in neonatal 6-OHDA-lesioned rats, and that a D1 agonist acts via the 5-HT1C receptors. Therefore, induction of oral activity by DA agonists occurs through a serotoninergic neurochemical system.
 ...
PMID:Serotonin (5-HT) systems mediate dopamine (DA) receptor supersensitivity. 831 65

The effect of the 5-HT1A receptor partial agonist tandospirone on memory was investigated in mice using a single trial, step-through passive avoidance task. Tandospirone disrupted performance in a dose-dependent manner when administered before the training trial but not when injected immediately post-training. The pre-training effect was not the result of reduced responsiveness to foot shock because tandospirone did not alter current threshold intensity to elicit flinch, run and vocalization responses. The performance deficit was alleviated by treatment with d-amphetamine prior to the retention test. The memory impairment by tandospirone was mimicked by the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-dipropylaminotetralin HBr) and blocked by the 5-HT1A receptor antagonist BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol-[4]- decane-7,9-dione). BMY7378 alone was ineffective. Treatment with the 5-HT synthesis inhibitor PCPA (parachlorophenylalanine) resulted in apparent enhancement rather than disruption of the avoidance behavior. However, the anterograde amnestic effects of tandospirone and 8-OH-DPAT were not affected by PCPA, and lack of interactions between PCPA and the 5-HT1A agonists revealed in the statistical analyses indicated that the effects of PCPA were not mediated by 5-HT1A receptors. It is concluded that 5-HT1A receptor agonists and partial agonists produce a reversible anterograde amnesia that is mediated by postsynaptic 5-HT1A receptors.
 ...
PMID:5-HT1A receptor agonists induce anterograde amnesia in mice through a postsynaptic mechanism. 831 49

The effects of the muscarinic antagonists scopolamine HBr and MeBr, the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the N-methyl-d-aspartate (NMDA) antagonists MK-801 and CGS-19755 on performance of rats in a delayed matching-to-position task were examined. Pretreatment with scopolamine HBr (0.05 and 0.1 mg/kg), resulted in a delay-dependent decrease in the percentage of correct responses and discriminability (log d), but had no effect on either the latency to complete trials, or the rate of trial completion during the fixed duration session. Scopolamine MeBr (0.1 mg/kg) did not impair percent correct or increase the response latency but did decrease the rate of trial completion. 8-OH-DPAT (up to 0.3 mg/kg), had no effect on percent correct, but did induce a small decrease in discriminability. The impairment in discriminability occurred only at a dose that substantially reduced the rate of trial completion. Both MK-801 (0.05 mg/kg) and CGS 19755 (10 mg/kg) induced a delay-independent impairment in percent correct, discriminability and a reduction in the rate of trial completion without affecting latency. A lower dose of CGS 19755 (5.0 mg/kg) induced a slight impairment in discriminability without significantly affecting the other measures. Taken together, these results demonstrate some dissociation between drug-induced cognitive and motor/motivational deficits in the DMTP test. However, the data question the specificity of putative cognitive impairments reported in many previous studies with the 5-HT1A agonist 8-OH-DPAT.
 ...
PMID:Dissociation between cognitive and motor/motivational deficits in the delayed matching to position test: effects of scopolamine, 8-OH-DPAT and EAA antagonists. 874 96

SM-9018 (cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl) hexahydro-1 H-isoindole-1,3(2H)-dione HCl) is a potential atypical antipsychotic with high affinity for 5-HT2, dopamine D2 and 5-HT1A receptors. Northern blot analysis was performed to compare the effects of SM-9018 and of haloperidol on the striatal c-fos mRNA expression in rats. Haloperidol (0.3-30 mg/kg, p.o.) markedly increased the striatal c-fos mRNA levels (about eight-fold at 30 mg/kg), the increase being abolished by lesioning of dopamine neurons with 6-hydroxydopamine. In contrast, SM-9018 produced only a slight increase (about two-fold) in c-fos mRNA expression at doses up to 30 mg/kg (p.o.). The 5-HT2 receptor antagonist, ritanserin (0.1-3 mg/kg, i.p.), dose-dependently attenuated the haloperiodol-induced c-fos expression, but the putative 5-HT1A receptor antagonist, NAN-190 (1-(2-methoxyphenyl)-4-(4-(2-phethalimmido)butyl)piperazine HBr; 1-10 mg/kg, i.p.), did not. These findings suggest that SM-9018 is weaker than haloperidol for induction of striatal c-fos mRNA expression, to which the 5-HT2 receptor blocking activity of SM-9018 seems to contribute.
 ...
PMID:Contrasting effects of SM-9018, a potential atypical antipsychotic, and haloperidol on c-fos mRNA expression in the rat striatum. 881 76

The (S)-enantiomer of 5-fluoro-8-hydroxy-2-(dipropylamino) tetralin [(S)-2a; (S)-UH301] was the first reported 5-HT1A receptor antagonist. We now give a full account on the synthetic effort leading to the preparation of the racemate and the enantiomers of 2a. The crystal and molecular structure of 2a. HBr has been determined by X-ray diffraction and the absolute configuration has been deduced using statistical tests of the crystallographic R values. The unit cell is tetragonal (P4(1)2(1)2) with a = b = 13.2235(2), c = 39.560(1) A and contains two crystallographically independent molecules in each asymmetric unit. The two solid state conformers differ in the conformation of the N-propyl groups. The pharmacological characterization of the enantiomers was done by use of in vivo biochemical and behavioural assays in rats. The (R)-enantiomer of 2a is a 5-HT1A receptor agonist of low potency while (S)-2a does not exhibit any agonist properties at 5-HT1A receptors. As a consequence of the opposing effects of the enantiomers, the racemate, rac-2a, does not produce any clear-cut effects in rats. The reduced efficacy of (S)-2a as compared to the well known 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino) tetralin (1;8-OH-DPAT) may be due to the fluoro-substituent induced negative potential of the aromatic ring.
 ...
PMID:Synthesis and pharmacology of the enantiomers of UH301: opposing interactions with 5-HT1A receptors. 902 53

To clarify the serotonergic mechanisms involved in the protection against ischemic neuronal damage, ZD-211 (citalopram HBr), a serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitor, or buspirone, a 5-HT1A agonist, was locally administered into the hippocampus of gerbils. Additionally, to clarify the role of the 5-HT nervous system in the hippocampus during ischemic neuronal damage, animals were subjected to the local administration of 5,7-dihydroxytryptamine (5,7-DHT), a 5-HT neurotoxin, before ischemia challenge. Gerbils received intrahippocampal administration of ZD-211 (200 nmol/animal) or buspirone (20 nmol/animal) before 5-min ischemia. 5,7-DHT was intrahippocampally administered 7 days before a 2-min non-lethal ischemia challenge. In vehicle-treated animals subjected to 5 min of ischemia, almost all hippocampal CA1 pyramidal neurons were lost. The treatment with ZD-211 or buspirone showed a significant protective effect, and the number of neurons was significantly increased compared to vehicle-treated animals. Pretreatment with NAN-190, a 5-HT1A antagonist, completely abolished the protective effect of ZD-211 or buspirone. In the 5,7-DHT-treated animals, the number of neurons was significantly reduced following 2 min of ischemia compared to vehicle-treated animals in which this period of ischemia is non-lethal. Thus, intrahippocampal treatment with ZD-211 or buspirone can protect neuronal damage following transient ischemia in gerbils. These effects of ZD-211 and buspirone were mediated through the 5-HT1A receptor in the hippocampus. Furthermore, the destruction of the 5-HT nervous system in the hippocampus aggravated ischemic neuronal damage. Therefore, this study showed that the enhanced activity of the 5-HT nervous system in the hippocampus may protect against neuronal damage following cerebral ischemia.
 ...
PMID:Role of hippocampal serotonergic neurons in ischemic neuronal death. 906 88

The effects of ionophoretically applied 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists were studied on rat nucleus tractus solitarius (NTS) neurones receiving unmyelinated vagal afferent input. 5-HT excited 15 of 34 neurones (44%), inhibited 10 (29%) and had no effect on nine. 8-Hydroxy-2-(di-N-propylamino)tetralin HBr (8-OH-DPAT) excited 23 of 53 neurones (43%), inhibited 24 (45%) and had no effect on six neurones and (+/-)-2,5-dimethoxy-4-iodoamphetamine HCl activated 18 of 37 neurones (49%), inhibited nine (24%) and had no effect on 10. These results demonstrate that activation of 5-HT1A and 5-HT2 receptors can excite or inhibit populations of NTS neurones. Phenylbiguanide, however, excited 20 of 23 neurones (87%), inhibited only one (4%) and had no effect on two indicating that 5-HT3 receptor activation has an excitatory action. NTS neurones receiving cardiac vagal afferent input were more likely to be excited by 5-HT (five of five, 100%) or 8-OH-DPAT (four of five. 80%) than the population as a whole. In conclusion, the data demonstrate that 5-HT1A, 5-HT2, and 5-HT3 receptor subtypes are functionally present on NTS neurones receiving excitatory vagal afferent input. Further, the subpopulation of NTS neurones receiving input from cardiac afferents are excited by 5-HT, possibly by an action on 5-HT1A or 5-HT3 receptors.
 ...
PMID:In vivo effects of 5-hydroxytryptamine receptor activation on rat nucleus tractus solitarius neurones excited by vagal C-fibre afferents. 922 74

A drug discrimination procedure was used to characterize the ethanol-like effects of a variety of 5-HT1 agonists. Previous studies found that the degree of substitution of the 5-HT1B/2C agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol. The present studies extend this initial finding to four additional 5-HT agonists with different selectivity for 5-HT1A, 5-HT1B, or 5-HT2C receptors: CGS 12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2a]quinoxaline maleate), mCPP [1-(3-chlorophenyl)piperazine diHCl], RU 24969 [5-methoxy-3(1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole succinate and 8-OH DPAT [(+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr]. Separate groups of rats were trained to discriminate 1.0 g/kg (n = 7), 1.5 g/kg (n = 6) or 2.0 g/kg (n = 8) ethanol from water. Following training, three to five doses of each 5-HT agonist were tested twice in each rat. The most selective 5-HT1B agonist tested, CGS 12066B (3-17 mg/kg; IP), completely substituted for the 1.0 g/kg ethanol, but not for 1.5 or 2.0 g/kg ethanol. Likewise, the 5-HT1B/2C agonist mCPP (0.56-1.7 mg/kg; IP) completely substituted only in the 1.0 g/kg ethanol training group. The 5-HT1A/1B agonist RU 24969 (0.1-3.0 mg/kg; IP) substituted for all training doses of ethanol, although in a lower proportion of the rats tested in the 2.0 g/kg ethanol training group. Finally, the 5-HT1A agonist 8-OH DPAT (0.1-1.0 mg/kg, IP) did not substitute completely for any ethanol training dose. The results consistently show that agonists with 5-HT1B activity produce discriminative stimulus effects similar to low and intermediate, but not high, ethanol training doses.
 ...
PMID:Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose. 934 79


<< Previous 1 2 3 Next >>