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

Drug interactions with 5-HT1 (5-hydroxytryptamine type 1) binding site subtypes were analyzed in rat frontal cortex. 8-Hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) displays high affinity (Ki 3.3 +/- 1 nM) for 29 +/- 3% of total [3H]5-HT binding in rat frontal cortex and low affinity (Ki 9,300 +/- 1,000) for 71 +/- 4% of the remaining 5-HT1 sites. Therefore, non-5-HT1A binding in rat frontal cortex was defined as specific [3H]5-HT binding observed in the presence of 100 nM 8-OH-DPAT. 5-Methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl) 1 H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), mianserin, and methysergide produce shallow competition curves of [3H]5-HT binding from non-5-HT1A sites. Addition of 10(-3) M GTP does not increase the apparent Hill slopes of these competition curves. Computer-assisted iterative curve fitting suggests that these drugs can discriminate two distinct subpopulations of non-5-HT1A binding sites, each representing approximately 35% of the total [3H]5-HT binding in the rat frontal cortex. All three 5-HT1 binding site subtypes display nanomolar affinity for 5-HT and 5-methoxytryptamine. A homogeneous population of 5-HT1A sites can be directly labeled using [3H]8-OH-DPAT. These sites display nanomolar affinity for 8-OH-DPAT, WB 4101, RU 24969, 2-(4-[4-(2-pyrimidinyl)-1-piperazinyl] butyl)-1,2-benzisothiazol-3-(2H)one-1, 1-dioxidehydrochloride (TVX Q 7821), 5-methoxydimethyltryptamine, and d-lysergic acid diethylamide. The potencies of RU 24969, TFMPP, and quipazine for [3H]5-HT binding are increased by addition of 100 nM 8-OH-DPAT and 3,000 nM mianserin to the [3H]5-HT binding assay. Moreover, the drugs have apparent Hill slopes near 1 under these conditions. This subpopulation of total [3H]5-HT binding is designated 5-HT1B. By contrast, methysergide and mianserin become more potent inhibitors of residual [3H]5-HT binding to non-5-HT1A sites in the presence of 100 nM 8-OH-DPAT and 10 nM RU 24969. The drug competition curves under these conditions have apparent Hill slopes of near unity and these sites are designated 5-HT1C. Drug competition studies using a series of 24 agents reveals that each 5-HT1 subtype site has a unique pharmacological profile. These results suggest that radioligand studies can be used to differentiate three distinct subpopulations of 5-HT1 binding sites labeled by [3H]5-HT in rat frontal cortex.
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PMID:Pharmacological differentiation and characterization of 5-HT1A, 5-HT1B, and 5-HT1C binding sites in rat frontal cortex. 294 38

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a serotonergic agonist with high affinity and selectivity for a particular population of central serotonin (5-HT) binding sites (i.e., 5-HT1A sites). Because the selectivity of 8-OH-DPAT may be due to the terminal amine substituents, the di-n-propyl analogue of 5-HT (i.e., 4) and of 5-methoxytryptamine (i.e., 5) were prepared and compared with 8-OH-DPAT with respect to their binding profile. Unlike 8-OH-DPAT, neither compound 4 nor 5 displays selectivity for 5-HT1A vs 5-HT2 sites. Consistent with these results, stimulus generalization occurs with 5 both in rats trained to discriminate 8-OH-DPAT from saline and in rats trained to discriminate the 5-HT2 agonist DOM from saline. The results of this study suggest that it is not the N,N-dipropyl groups that account for selectivity, but, rather, it is some feature associated with the pyrrole portion of the indolylalkanamines that is important.
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PMID:N,N-di-n-propylserotonin: binding at serotonin binding sites and a comparison with 8-hydroxy-2-(di-n-propylamino)tetralin. 296 44

Serotonin (5-HT) usually induced a slow hyperpolarization lasting several minutes on first drop-application onto CA1 neurons. Subsequent applications always caused a briefer (less than 2 min) hyperpolarization, usually followed by a depolarization. 8-Hydroxy-2(di-n-propylamino)tetralin, a 5-HT1A receptor agonist, and 5-methoxytryptamine, a 5-HT1 receptor agonist, produced only the long-lasting hyperpolarization. The application of 5-HT agonists caused a persistent prolongation of the post-spike train afterhyperpolarization. These observations suggest that the long-lasting hyperpolarization produced by 5-HT may be mediated by the activation of the 5-HT1A receptor subtype.
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PMID:Serotonin-1A receptor activation in hippocampal CA1 neurons by 8-hydroxy-2-(di-n-propylamino)tetralin, 5-methoxytryptamine and 5-hydroxytryptamine. 296 13

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective serotonin1A (5-HT1A) receptor agonist, was studied for its anti-immobility activity in the forced swimming test when administered into the raphe nuclei medianus and dorsalis of rats. At concentrations ranging from 0.5 to 5 micrograms, 8-OH-DPAT significantly reduced the immobility of rats when administered into the nucleus raphe dorsalis, but only 5 micrograms was effective when administered into the nucleus medianus. The activity of rats in an open-field under conditions identical to those used in the forced swimming test was not significantly changed by various concentrations of 8-OH-DPAT administered into the nucleus raphe dorsalis, but was significantly increased by an infusion of 5 micrograms 8-OH-DPAT into the nucleus raphe medianus. The effect of an infusion of 1 micrograms 8-OH-DPAT into the nucleus dorsalis was prevented by infusing 2.5 micrograms (-)-propranolol or 2.5 micrograms (-)-pindolol into the same area 5 min before 8-OH-DPAT or by treating the animals with sulpiride systemically (100 mg/kg i.p.) or centrally (in the nucleus accumbens; 1 microgram/0.5 microliter). The results suggest that 8-OH-DPAT reduces the immobility of rats by activating dopamine transmission, probably in the nucleus accumbens, as a consequence of its ability to reduce the activity of 5-HT neurons that originate in the nucleus raphe dorsalis. In view of the similarities between the effects of well-established antidepressants and 8-OH-DPAT in the forced swimming test, it is suggested that 5-HT1A receptor agonists may constitute a novel class of antidepressant agents.
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PMID:8-Hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis. 297 8

1. The functional significance of subtypes of 5-hydroxytryptamine (5-HT) receptors was studied in the rat spinal reflex pathway. 2. Ketanserin had no effect on the mono- (MSR) or polysynaptic reflex (PSR) in spinal rats, but decreased the PSR in intact rats. 3. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) decreased the MSR and increased the PSR in spinal rats. 4. Ketanserin antagonized the effects of 5-MeODMT without antagonizing the effects of 8-OH-DPAT. 5. Cinanserin had similar effects to those of ketanserin. 6. These results suggest that both 5-HT1A and 5-HT2 receptors mediate MSR inhibition and PSR augmentation in the spinal reflexes of spinal rats, and that the 5-HT2 receptor has a supraspinal tonic excitatory influence on the PSR in intact rats.
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PMID:Functional significance of subtypes of 5-HT receptors in the rat spinal reflex pathway. 297 87

Intracellular recordings were made from parasympathetic neurons of the rabbit vesical pelvic ganglia (VPG) maintained in vitro. 5-Hydroxytryptamine (5-HT) inhibited cholinergic transmission in the VPG by reducing the fast excitatory postsynaptic potential (EPSP) evoked by stimulations of pelvic nerves. 8-Hydroxy-2-(di-n-propyl-amino) tetralin hydrochloride mimicked the inhibitory effect of 5-HT on the ganglionic transmission. 5-HT-induced inhibition of the fast EPSP was antagonized by spiperone. The results suggest that 5-HT1A receptor subtypes mediate the inhibition of cholinergic transmission in the rabbit VPG.
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PMID:5-hydroxytryptamine inhibits cholinergic transmission through 5-HT1A receptor subtypes in rabbit vesical parasympathetic ganglia. 337 Apr 57

1 A study has been made of the pharmacology of 5-hydroxytryptamine (5-HT)-induced hyperpolarization responses recorded extracellularly from the rat isolated superior cervical ganglion (SCG). 2 Hyperpolarization responses induced by 5-HT (1 X 10(-8)-1 X 10(-4) M) in the presence of MDL 72222 (1 X 10(-5) M) were not antagonized by phentolamine (1 X 10(-6) M), prazosin (1 X 10(-7)-3 X 10(-7) M), haloperidol (1 X 10(-6) M) or ketanserin (1 X 10(-7)-1 X 10(-6) M). However, the latter two compounds both potentiated and increased the persistence of the hyperpolarization induced by moderate to high concentrations of 5-HT. Spiperone (1 X 10(-7) M) caused similar effects. All further experiments were performed in the presence of ketanserin (1 X 10(-6) M) as well as MDL 72222. 3 8-Hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT; 1 X 10(-7)-1 X 10(-4) M) and ipsapirone (3 X 10(-5)-3 X 10(-4) M) behaved as weak hyperpolarizing agonists on the SCG. However, at concentrations below those required to produce hyperpolarization, both compounds acted as unsurmountable antagonists of 5-HT-induced hyperpolarization. 4 5-Carboxamidotryptamine (5-CT; 1 X 10(-9)-1 X 10(-5) M) mimicked the hyperpolarizing activity of 5-HT on the SCG. The EC50 for 5-CT was approximately 9 fold lower than that for 5-HT. 5 Spiperone (1 X 10(-7) - 1 X 10(-5) M) behaved as a reversible competitive antagonist of hyperpolarization responses induced by 5-HT with a pKB value of 7.40 +/- 0.09. Spiperone (1 X 10(-7)-1 X 10(-6) M) also caused concentration-dependent rightward displacement of the 5-CT concentration-hyperpolarization response curve. In this case, the pKB was 7.80 +/- 0.05. 6 (+/-)-Cyanopindolol (3 X 10(-7)-3 X 10(-6) M) caused non-parallel rightward displacements of the 5-HT concentration-response curve. Against 5-CT, (+/-)-cyanopindolol (3 X 10(-7)-3 X 10(-6) M) caused a concentration-independent rightward displacement of the concentration-response curve, accompanied by a large increase in the maximum response. 5-CT-induced hyperpolarization recorded in the presence of (+/-)-cyanopindolol (3 X 10(-7) M) was not significantly antagonized by methiothepin (1 X 10(-6) M) or methysergide (1 X 10(-6) M). 7. It is concluded that 5-HT-induced hyperpolarization of the rat SCG is mediated via a 5-HT1-like receptor which resembles the 5-HT1A binding site. However, a lack of selective drugs precludes more definitive characterization of this receptor.
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PMID:Pharmacological characterization of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion. 367 2

In the rat inferior vena cava preincubated with 3H-noradrenaline, the effects of nine serotonin (5-HT) receptor agonists and of eight antagonists (including two beta-adrenoceptor blocking agents) on the electrically evoked 3H overflow were determined. 1. 5-HT, 5-carboxamido-tryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969), 5-methoxytryptamine, N,N-dimethyl-5HT, tryptamine and 5-aminotryptamine inhibited the evoked 3H overflow. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT1B binding sites, but not with their affinities for 5-HT1A, 5-HT1C or 5-HT2 binding sites. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, and ipsapirone, a partial agonist at these receptors, did not inhibit overflow. 2. Cyanopindolol facilitated the evoked 3H overflow, an effect which was abolished by propranolol. The maximum inhibition of overflow obtainable with 5-HT was diminished by cyanopindolol. 3. The concentration-response curve for 5-HT was shifted to the right by metitepine, metergoline, quipazine, 6-chloro-2-(1-piperazinyl)pyrazine (MK 212) and propranolol which, given alone, did not affect 3H overflow. The apparent pA2 values of these antagonists tended to be correlated with their affinities for 5-HT1B (but not 5-HT1A, 5-HT1C or 5-HT2) binding sites. Ketanserin, a 5-HT2 receptor antagonist, and spiperone, which blocks 5-HT2 and 5-HT1A but not 5-HT1B or 5-HT1C receptors, failed to antagonize the effect of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava. 368 95

(1S,2R)-8-Hydroxy-1-methyl-2-(dipropylamino)tetralin [(1S,2R)-3] has been previously characterized as a selective and potent but partial 5-HT1A-receptor agonist. In the present study, we have prepared derivatives of (1S,2R)- and (1R,2S)-3 in which various C8-substituents have been introduced. In addition, the enantiomers of the N-isopropyl-N-n-propylamino derivative of 3 were prepared. The new derivatives were tested in vivo by use of behavioral and biochemical tests in rats. In addition, the affinity of the compounds was studied by competition experiments with [3H]-8-OH-DPAT in rat brain tissue. The only new derivative which behaved like a selective 5-HT1A-receptor agonist was the C8-carboxamide derivative (1S,2R)-13. The other active derivatives, including (1S,2R)-3, have more complicated pharmacological profiles and may be best characterized as mixed 5-HT1A-receptor agonists/dopamine D2-receptor antagonists.
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PMID:Derivatives of cis-2-amino-8-hydroxy-1-methyltetralin: mixed 5-HT1A-receptor agonists and dopamine D2-receptor antagonists. 753 Jul 73

The object exploration task allows the measure of changes in locomotor and exploratory activities, habituation, and reaction to a spatial change and to novelty. The effects of intrahippocampal (dorsal CA1 field) microinjections of serotonin 1 receptor (5-HT1) agonists on these behavioral components were evaluated in the rat. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 5 micrograms/microliters) was used as a 5-HT1A agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93,129,16 micrograms/microliters) as a 5-HT1B agonist, and scopolamine (10 micrograms/microliters) as a muscarinic cholinergic antagonist. Scopolamine induced a long-lasting increase in locomotor activity and a lack of reaction to spatial change; both these results are in agreement with the known crucial influence of the septo-hippocampal cholinergic system in hippocampal functioning. Stimulation of 5-HT1A and 5-HT1B receptors induced a decrease in object exploration and habituation without affecting the retrieval of spatial information. But stimulation of hippocampal 5-HT1B receptors induced a selective change in the animal's emotional state, i.e., an initial decrease in locomotor activity and a neophobic reaction in response to a new object; such effects did not occur following stimulation of 5HT1A receptors. These results have to be considered in the light of the anxiogenic property of 5-HT1B agonists. On the whole, they support the hypothesis of the involvement of the serotonergic system, via 5HT1A and 5-HT1B receptors, in the modulation of hippocampal functions.
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PMID:Changes in exploratory activity following stimulation of hippocampal 5-HT1A and 5-HT1B receptors in the rat. 755 Jun 15


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