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At least 19 recordsLinked to original sources
PubMed1995

The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors.

1. Full length clones of the human 5-HT2B receptor were isolated from human liver, kidney and pancreas. The cloned human 5-HT2B receptors had a high degree of homology (approximately 80%) with the rat and mouse 5-HT2B receptors. 2. PCR amplification was used to determine the tissue distribution of human 5-HT2B receptor mRNA. mRNA encoding the 5-HT2B receptor was expressed with greatest abundance in human liver and kidney. Lower levels of expression were detected in cerebral cortex, whole brain, pancreas and spleen. Expression was not detected in heart. 3. Northern blot analysis confirmed the presence of 5-HT2B receptor mRNA (a 2.4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized band of hybridization was detected in liver and kidney. This raises the possibility of a splice variant of the receptor or the presence of an additional homologous receptor. 4. The human 5-HT2B receptor was expressed in Cos-7 cells and its ligand binding characteristics were compared to similarly expressed human 5-HT2A and 5-HT2C receptors. The ligand specificity of the human 5-HT2B receptor (5-HT > ritanserin > SB 204741 > spiperone) was distinct from that of the human 5-HT2A (ritanserin > spiperone > 5-HT > SB 204741) and 5-HT2C (ritanserin > 5-HT > spiperone = SB 204741) receptors. On the basis of a higher affinity for ketanserin and a lower affinity for yohimbine the human 5-HT2B receptor also appeared to differ from the rat 5-HT2B receptor. 5. These findings confirm the sequence of the human 5-HT2B receptor and they demonstrate that the receptor has a widespread tissue distribution. In addition, these data suggest that there are differences in ligand affinities between different species homologues of the receptor. Finally, the finding of two distinct bands on the Northern blots of liver and kidney raises the possibility of splice variants or subtypes of 5-HT2B receptors, within these tissues.

3T3 Cells↗
PubMed1995

5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity.

The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pKI 8.0) and 5-HT2B receptors (pA2 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pKI < 6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pKB 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

Administration, Oral↗
PubMed1995

5-Hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats.

Vascular responsiveness to 5-hydroxytryptamine (5-HT) is dramatically increased in hypertension. The hypothesis that augmented vasoconstriction to 5-HT in hypertension is due to a change in receptor subtype on vascular myocytes was tested. Mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive (systolic blood pressure > 180 mm Hg) and sham normotensive (systolic blood pressure < 130 mm Hg) rats were mounted in isolated tissue baths for measurement of isometric contractile force. The receptor mediating contraction in isolated mesenteric arteries from sham and DOCA-salt hypertensive rats is a member of the 5-HT2 family based on rank order of agonist potency (5-HT = alpha-methyl-5-HT [5-HT2 receptor agonist]>tryptamine>5-hydroxykynuramine). 5-HT was approximately 10-fold more potent in contracting mesenteric arteries from DOCA-salt hypertensive rats compared with arteries from sham normotensive rats. The tryptophan metabolite kynuramine, which possesses significant contractile activity at the 5-HT2B receptor, contracted hypertensive arteries significantly (50% of 5-HT maximum) but not sham arteries. Ketanserin (5-HT2A antagonist) competitively inhibited contraction to 5-HT in arteries from normotensive rats (-log dissociation constant [mol/L]; pKB = 8.54) but not from hypertensive rats (pKB > 6.5). Moreover, contraction to kynuramine was not blocked by ketanserin. Thus, under normal conditions, 5-HT2A receptors mediate contraction to 5-HT. However, in DOCA-salt hypertension, ketanserin-insensitive 5-HT2 receptors, possibly 5-HT2B receptors, mediate mesenteric arterial contraction to 5-HT.

Algorithms↗
PubMed1994

The mouse 5-HT2B receptor: possible involvement in trophic functions of serotonin.

The novel serotonin receptor 5-HT2B shows the highest homology to the 5-HT2 family of receptors. The pharmacological profile of membranes from 5-HT2B cDNA stably transfected LMTK- cell line, corresponds to a new 5-HT2-like receptor named 5-HT2B, although some difference exists between the mouse and rat pharmacology. A similar pharmacological profile is detected on the immortalized teratocarcinoma-derived cell line 1C11 upon 2 days of serotoninergic differenciation by cAMP. In both cell lines, the analysis 125I-DOI binding reveals the presence of a single class of sites, the affinity of which is one order of magnitude lower than the one reported for the 5-HT2A receptor. This demonstrates that the 5-HT2B receptor is functionally expressed before the complete serotoninergic differentiation of 1C11 cells. These observations are in good agreement with the presence of 5-HT2B mRNA in early mouse embryonic development. Furthermore, the major sites of 5-HT2B mRNA embryonic expression are in the heart, and in the neural fold before the closure of the neural tube. Therefore, this receptor could account at least in part for the trophic functions attributed to the 5-HT2-like receptors.

Animals↗
PubMed1989

Differentiation of 5-hydroxytryptamine2 receptor subtypes using 125I-R-(-)2,5-dimethoxy-4-iodo-phenylisopropylamine and 3H-ketanserin.

The radioligand binding characteristics of 125I-R-(-)4-iodo-2,5-dimethoxyphenylisopropylamine [125I-R-(-)DOI] and 3H-ketanserin were compared in rat and bovine cortical membranes. In rat cortex, 125I-R-(-)DOI labels a relatively low density of binding sites (Bmax = 2.5 +/- 0.2 pmol/gm tissue) with high affinity (KD = 0.63 +/- 0.09 nM). In bovine cortex, specific binding of 125I-R-(-)DOI represents less than 20% of total binding at radioligand concentrations above 0.6 nM, and, therefore, the data cannot be analyzed adequately by Scatchard transformation. By contrast, 3H-ketanserin displays saturable, specific high-affinity binding in both rat cortex (KD = 1.0 +/- 0.1 nM; Bmax = 11 +/- 0.4 pmol/gm tissue) and bovine cortex (KD = 1.2 +/- 0.2 nM; Bmax = 5.3 +/- 0.4 pmol/gm tissue). Ki values for 30 drugs were determined for 125I-R-(-)DOI-labeled sites in rat cortex and 3H-ketanserin-labeled sites in bovine cortex. 5-Hydroxytryptamine (5-HT) displays 250-fold higher selectivity for the 125I-R-(-)DOI-labeled sites (Ki = 3.0 +/- 0.7 nM) than for the 3H-ketanserin-labeled sites (Ki = 750 +/- 50 nM). Structural congeners of R-(-)DOI display 80- to 160-fold higher affinity for the 125I-R-(-)DOI binding site than for the 3H-ketanserin-labeled binding site. d-LSD and putative 5-HT2 antagonists are approximately equipotent at both sites. Significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and putative 5-HT2A sites labeled previously by 77Br-R-(-)DOB (r = 0.93, p less than 0.01), putative 5-HT2B sites labeled by 3H-ketanserin in bovine cortex (r = 0.63, p less than 0.01), and 5-HT1C binding sites that have been characterized by other investigators (r = 0.78, p less than 0.01). No significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and 5-HT1A, 5-HT1B, 5-HT1D, or 5-HT3 sites, as determined by previous investigators. We conclude that 125I-R-(-)DOI labels a novel 5-HT binding site subtype (tentatively designated the 5-HT2A binding site) that is present in rat cortex but is either absent or minimally present in bovine cortex. By contrast, 3H-ketanserin labels both the putative 5-HT2A site in rat cortex as well as a separate, distinct recognition site that is present in both rat and bovine cortex, tentatively designated the 5-HT2B site.

Amphetamines↗
PubMed1995

(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7- bc][2,6]-naphthyridine: a 5-HT2C/2B receptor antagonist with low 5-HT2A receptor affinity.

The indolonaphthyridine 8 is described as a selective 5-HT2C/2B vs 5-HT2A receptor antagonist. The compound was synthesized in seven steps starting from indoline and isonicotinic acid chloride. The key step is a photocyclization of the indolinyl tetrahydropyridinocarbamic acid ethyl ester 4 to the cis-octahydroindolo[1, 7-bc][2,6]naphthyridinecarbamic acid ethyl ester 5. The synthesis was accomplished by reduction with aluminum hydride and racemic resolution. The indolonaphthyridine 8 exerted the binding profile of a selective 5-HT2C receptor ligand (pKD 7.8) and behaved as an antagonist on the 5-HT-induced accumulation of inositol phosphates in pig choroid plexus cells (pKB 7.13). Compound 8 dose-dependently inhibited the ACTH response to MK-212 in rats and the MK-212-induced hypophagic effect with an ID50 value of 0.3 mg/kg sc. Compound 8 acted as a 5-HT2B receptor antagonist at the rat stomach fundus with a pKB value of 7.34.

Animals↗
PubMed1995

Functional serotonin-2B receptors are expressed by a teratocarcinoma-derived cell line during serotoninergic differentiation.

Among immortalized teratocarcinoma-derived cells, the clone 1C11 is a committed precursor of the neuronal lineage. On day 2 of its serotoninergic differentiation, this clone expresses only one subtype of serotonin [5-hydroxytryptamine (5-HT)] receptor, which is functionally coupled to phosphatidylinositol hydrolysis. The identity of these receptors was established by comparing their properties with those of 5-HT2B receptors expressed by LMTK- fibroblasts stably transfected with the recently cloned murine cDNA NP75 (LM5 cells). In both cell types, the analysis of (+/-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)- 2-aminopropane HCl ([125I]DOI) binding revealed the presence of a single class of sites, the affinity of which was 1 order of magnitude lower than that reported for 5-HT2A receptors. In 1C11 cells differentiated for 2 days, as well as in LM5 cells, DOI binding was decreased by nonhydrolyzable analogs of GTP, indicating that the 5-HT2B receptor is functionally coupled to a G protein. The DOI-induced increase of phosphoinositide hydrolysis, which was correlated with both GTPase activity and binding data, is mediated by a Gq protein. This work demonstrates that the 5-HT2B receptor is functionally expressed before complete serotoninergic differentiation of 1C11 cells. The inducible 1C11 clone thus provides an in vitro model to investigate the possible role of the 5-HT2B receptor in the expression of the serotoninergic phenotype.

Animals↗
PubMed1994

Evidence that 5-HT2c receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety.

Four non-selective 5-HT2C/5-HT2A receptor antagonists, mianserin (2-8 mg/kg), 1-naphthyl piperazine (1-NP) (0.5-1 mg/kg), ICI 169,369 (20 mg/kg) and LY 53857 (5 mg/kg), increased punished responding for a food reward in the rat Geller-Seifter test 30 min after subcutaneous (SC) administration. This property was shared by the benzodiazepine anxiolytic chlordiazepoxide (5 mg/kg SC). However, the selective 5-HT2A receptor antagonists ketanserin (0.2-1 mg/kg SC) and altanserin (0.5, 1 mg/kg SC) had little effect. The 5-HT1A, 5-HT1B and beta-adrenergic receptor antagonists pindolol and cyanopindolol (6 mg/kg SC) did not affect punished responding either, nor did the 5-HT1D receptor partial agonist and alpha 2 adrenergic receptor antagonist yohimbine (2.5 mg/kg SC) or the histamine H1 receptor antagonist mepyramine (1 mg/kg SC). Unpunished responding was also modestly increased after some doses of the 5-HT2C/5-HT2A receptor antagonists. However, this effect was inconsistent and was also seen after chlordiazepoxide. Furthermore, it was not associated with the increase in punished responding observed in rats orally treated with mianserin (10, 20 mg/kg), 1-NP (10, 20 mg/kg) or ICI 169,369 (50 mg/kg). The action of the 5-HT2C/5-HT2A receptor antagonists tested is therefore consistent with anxiolysis. The results also strongly suggest that this effect is mediated by blockade of the 5-HT2C receptor, although the possibility of 5-HT2B receptor mediation is discussed.

Administration, Oral↗
PubMed1995

Mediation by 5-hydroxytryptamine2B receptors of endothelium-dependent relaxation in rat jugular vein.

1. An 'atypical' 5-HT2 receptor which is located on the endothelium of rat jugular vein has been described. In the present study we have further defined the nature of the 5-HT2 receptor subtype present in this preparation. 2. In experiments conducted in the presence of ketanserin to preclude involvement of 5-HT2 receptors, the mixed 5-HT2B/2C antagonist, SB 200646, acted as an antagonist of 5-HT at the endothelial 5-HT receptor (pA2 = 7.2). Yohimbine, which exhibits negligible affinity for rat 5-HT2C receptors but has high 5-HT2B receptor affinity, acted as a potent but non-surmountable antagonist (pA2 > or = 7.3) in rat jugular vein. Neither yohimbine nor SB 200646 affected endothelium-dependent relaxations induced by carbachol. 3. Mianserin also acted as a surmountable antagonist (pA2 = 7.3) and the 5-HT2B agonist, BW 723C86, acted as a potent partial agonist (pEC50 [95% C L], intrinsic activity +/- s.e. mean = 7.9 [7.6-8.3], 0.84 +/- 0.04). Responses to BW 723C86 were antagonized by SB 200646 (0.3 microM) yielding an 'apparent' pA2 [95% CL] of 7.03 [6.76-7.32]. 4. These data are consistent with the presence of 5-HT2B receptors mediating endothelium-dependent relaxation of rat jugular vein.

Animals↗
PubMed1995

Expression of serotonin receptor mRNAs in blood vessels.

Using RT-PCR we distinguished mRNAs for all known G-protein coupled serotonin receptors expressed in various rat and porcine blood vessels. Nearly all vessels expressed 5HT1D beta, 5-HT2A, 5-HT2B, 5-HT4, and 5-HT7 receptor mRNA to different extents. New splice variants of the porcine 5-HT4 receptor were observed. Similar PCR assays were performed with endothelial and smooth muscle cells from human pulmonary artery, aorta, and with endothelial cells from human coronary artery and umbilical vein. All endothelial cells expressed 5-HT1D beta, 5-HT2B, and 5-HT4 receptor mRNA, whereas in smooth muscle cells 5-HT1D beta, 5-HT2A, 5-HT7, and in some experiments 5-HT2B receptor mRNA were found. A model for the regulation of vascular tone by different 5-HT receptors is proposed.

Amino Acid Sequence↗
PubMed1990

Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes.

Affinities of drugs for 21 indolealkylamine derivatives, some with putative hallucinogenic activity, were determined at 5-HT1A, 5-HT2A and 5-HT2B recognition sites, using radioligand competition studies. Nearly all of the derivatives displayed greatest potency for the 5-HT2A receptor, labelled by [125I]R-(-)DOI in the cortex of the rat. Most derivatives displayed 2-10 times lower affinity at the HT2B receptor labelled by [3H]ketanserin in bovine cortex. Derivatives lacking ring substituents displayed lower affinities for all of the recognition sites, compared to derivatives substituted in the 4- or 5-position of the indole ring. The 4-hydroxylated derivatives displayed 25-380-fold selectivity for the 5-HT2A site, vs the 5-HT1A site, while the 5-substituted derivatives displayed approximately equal potency at the 5-HT1A and 5-HT2A sites. Affinity of all the compounds at the 5-HT2B site was greater than 300 nM. The 6-substituted derivatives displayed greater than micromolar affinities for all of the 5-HT recognition sites examined. The size of the N,N-dialkyl substituent was a secondary determinant of affinity, with groups larger than N,N-diisopropyl resulting in a marked reduction in affinity at both the 5-HT2A and 5-HT1A recognition sites. This study demonstrated that hallucinogenic 4-hydroxy-indolealkylamines, like psychotomimetic phenylisopropylamines, bind potently and selectively to the 5-HT2A recognition site, labelled by [125I]R-(-)DOI. This provides further evidence indicating that this recently described subtype of the 5-HT2 receptor may partially mediate the action of hallucinogenic agents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

5-hydroxytryptamine2A, 5-hydroxytryptamine2B, and 5-hydroxytryptamine2C receptor mRNA expression in the spinal cord of rat, cat, monkey and human.

Currently three subtypes of the 5-HT2 receptor have been identified through binding studies and/or molecular biology studies, 5-HT2A, 5-HT2B, and 5-HT2C. The identification of these receptor subtypes in the spinal cord of humans and experimental animal species is incomplete. In the present study, polymerase chain reaction with Southern hybridization analysis was used to determine whether the mRNA for the 5-HT2A, 5-HT2B and 5-HT2C receptors could be detected in spinal cord tissue from rats, cats, monkeys and humans. Brain tissue from rat, cat and monkey were also examined for comparison. 5-HT2A and 5-HT2B receptor mRNAs were amplified and localized with rat 5-HT2A and 5-HT2B primers and probes, respectively, in tissue from all species. In rats, 5-HT2C receptor mRNA was amplified and localized with rat 5-HT2C primer and mouse 5-HT2C probe, respectively, while in cat, monkey, and human tissue, human 5-HT2C primers and probes were used. Spinal cord from all four species contained mRNA for the 5-HT2A receptor. Brain tissue from rat, cat and monkey also contained 5-HT2A mRNA. Spinal cord tissue from all four species contained 5-HT2B message. Brain tissue from cat and monkey contained 5-HT2B mRNA, but this was not detected in rat brain. 5-HT2C mRNA was detected in spinal cord and brain tissue from rat, monkey and human, but was only detected in brain tissue of the cat (i.e. no 5-HT2C mRNA was detected in cat spinal cord).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist.

1. SB 200646A, N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride, the first reported selective 5-HT2C/2B over 5-HT2A receptor antagonist, (pK1 rat 5-HT2C receptor 6.9, pA2 rat 5-HT2B receptor 7.5, pK1 rat 5-HT2A receptor 5.2) dose-dependently blocked a putative rat model of 5-HT2C receptor activation; 1-(3-chlorophenyl)piperazine (mCPP, 5 mg kg-1, i.p. 20 min pretest)-induced hypolocomotion (estimated ID50 19.2 mg kg-1, p.o.). 2. SB 200646A also blocked another putative in vivo model of 5-HT2C receptor function; mCPP (5 mg kg-1, i.p. 20 min pretest)-induced hypophagia in 23 h food-deprived rats (estimated ID50 18.3 mg kg-1, p.o.). 3. SB 200646A did not antagonize 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shakes in rats at doses up to 200 mg kg-1, p.o., an effect thought to be mediated by 5-HT2A receptors for which SB 200646A has its next highest affinity (50 fold less) after the 5-HT2C and 5-HT2B sites. 4. SB 200646A (20, 40 mg kg-1, p.o., 1 h pretest) also reversed mCPP (0.5 mg kg-1, i.p., 30 min pretest)-induced anxiety in the social interaction test, under low light familiar conditions. 5. When given alone, under high light unfamiliar conditions, SB 200646A (2-40 mg kg-1, p.o.) increased active social interaction without affecting locomotor activity in the rat social interaction test. This is consistent with an anxiolytic action of SB 200646A. 6. These results indicate that SB 200646A has in vivo efficacy and that 5-HT2C or 5-HT2B receptors are indeed likely to mediate mCPP-induced hypolocomotion, hypophagia and anxiogenesis. They also suggest that 5-HT2C,2B receptor blockade induces anxiolysis.

Animals↗
PubMed1995

Functional evidence for a 5-HT2B receptor mediating contraction of longitudinal muscle in human small intestine.

Application of 5-hydroxytryptamine induces contraction of longitudinal muscle strips from human terminal ileum. The response was resistant to antagonism by ketanserin, ondansetron or DAU6285, but was non-surmountably antagonized by methysergide. The selective 5-HT2B/2C receptor antagonist, SB 200646A evoked a concentration-dependent, parallel and dextral displacement of the concentration-response curve to 5-HT, yielding a pA2 estimate of 7.17. Application of yohimbine, a 5-HT1 and 5-HT2B receptor antagonist, also induced a rightward shift of the response curve to 5-HT, yielding a pA2 estimate of 8.10. In conclusion, it appears that a 5-HT2B receptor mediates the contractile response of the longitudinal muscle of human small intestine to 5-HT.

Acetylcholine↗
PubMed1995

Characteristics of [3H]5-hydroxytryptamine binding to iris-ciliary body tissue of the rabbit.

PURPOSE: This study sought to identify, characterize, and localize subtypes of 5-hydroxytryptamine (HT) receptors in rabbit iris-ciliary body. METHODS: Radioligand binding assays were performed with [3H]5-hydroxytryptamine on membranes prepared from rabbit iris-ciliary bodies and on tissue sections subsequently developed by autoradiography. RESULTS: [3H]5-HT appeared to bind to a single population of receptors in membrane preparations of rabbit iris-ciliary body. The apparent affinity of the ligand (KD) was 2.19 nM, and the density of binding sites was 58.3 fmol/mg protein. Binding of [3H] 5-HT exhibited guanosine-5-triphosphate sensitivity. Competitive inhibition experiments were performed to differentiate between 5-HT receptor subtypes. A relative potency order of 5-CT > 5-HT = 8-OH-DPAT > ipsapirone > RU24969 > sumatriptan > ritanserin > ketanserin was demonstrated. The apparent inhibitory constants for the ligands tested fit with the profile expected of binding to 5-HT1A receptors. Inhibition studies with [3H] 5-HT plus 100 nM 8-OH-DPAT (which inhibits binding to 5-HT1A receptors only) representing total binding, indicated that no further displacement occurred when ligands preferentially selective for 5-HT1B, 5-HT1D alpha,1D beta, or 5-HT2C were tested. Total binding of [3H] 5-HT in tissue sections developed by autoradiography was displaced completely by 100 nM 8-OH-DPAT. Melatonin showed little affinity for the [3H] 5-HT binding sites. CONCLUSIONS: A population of 5-HT1A receptors is present in rabbit ciliary processes. There is no evidence to suggest the presence of 5-HT1D alpha, 5-HT1D beta, 5-HT2B, or 5-HT2C receptors in the iris-ciliary body.

Animals↗
PubMed1995

[5-hydroxytryptamine (serotonin) receptors--nomenclature and classification of types and subtypes].

5-HT receptors represent a superfamily of receptors with the largest known number of receptor subtypes. At present 15 receptor subtypes of three groups has been recognized. The 5-HT1 subfamily of receptors contains subtypes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F; activation of all of them results in the inhibition of adenylylcyclase. The subfamily of 5-HT2 contains subtypes 5-HT2A, 5-HT2B, and 5-HT2C; their activation leads to the stimulation of PLC. Finally, subfamily of miscellaneous 5-HT receptors contains subtypes 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7; some of them has been cloned, however, our knowledge on their function is still minimal. 5-HT receptors participate in many physiological functions and a disturbance in serotonergic neurotransmission might cause several types of disease. 5-HT plays an important role in depression; to cure this disease, drugs which increase levels of this neurotransmitter are used. A new drug group called Selective Serotonin Reuptake Inhibitors (SSRI) has been recently discovered. These drugs block the reuptake of 5-HT into nerve endings. There is an intensive search for new selective agonists as well as antagonists which could be use not only in the classification of receptor subtypes but which also possess certain therapeutic potential.

Animals↗
PubMed1995

Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.

Alcoholism↗