Morales, Marisela, Wang, Shwun-De
Differential Composition of 5-Hydroxytryptamine3 Receptors Synthesized in the Rat CNS and Peripheral Nervous System
J. Neurosci. 2002 22: 6732-6741
"The type 3 serotonin (5-HT3) receptor is the only ligand-gated ion channel receptor for serotonin in vertebrates. Two 5-HT3 receptor subunits have been cloned, subunit A (5-HT3A) and subunit B (5-HT3B). We used in situ hybridization histochemistry and reverse transcriptase-PCR amplification to demonstrate that 5-HT3A subunit transcripts are expressed in central and peripheral neurons. In contrast, 5-HT3B subunit transcripts are restricted to peripheral neurons. Thus, the prevalent form of 5-HT3 receptor synthesized within the CNS lacks the 5-HT3B subunit. Because coexpression of 5-HT3A and 5-HT3B subunits produces heteromeric 5-HT3A/3B receptors with properties that differ from those of 5-HT3A homomeric receptors, we investigated possible coexpression of both subunits at the cellular level. We found that near to 90% of all 5-HT3B expressing neurons coexpress the 5-HT3A subunit in superior cervical and nodose ganglia (NG). In addition, there is a cellular population that expresses only the 5-HT3A subunit. Therefore, peripheral neurons have the capacity to synthesize two different 5-HT3 receptors, 5-HT3A+/3B and 5-HT3A+/3B+ receptors. We also determined that neurons of NG projecting to the nucleus tractus solitarium and those of dorsal root ganglia projecting to superficial layers of the spinal cord express 5-HT3A or 5-HT3A/3B subunits. Thus, presynaptic 5-HT3 receptors containing the 5-HT3B subunit might be present in these target brain areas. The compartmentalized structural composition of the 5-HT3 receptor may be the basis of functional diversity within this receptor. This raises the possibility that 5-HT3 receptors participating in sympathetic, parasympathetic and sensory functions may be functionally different from those involved in cognition and emotional behavior." [Abstract]

Kelley SP, Bratt AM, Hodge CW.
Targeted gene deletion of the 5-HT(3A) receptor subunit produces an anxiolytic phenotype in mice.
Eur J Pharmacol 2003 Feb 7;461(1):19-25
"Anxiety disorders are the most common psychiatric disorders. Typical medications used to treat patients are benzodiazepines or antidepressants that target serotonin (5-HT) activity. The ionotropic 5-HT(3) receptor has emerged as a potential therapeutic target because selective antagonist compounds reduce anxiety in rodents, primates, and humans. 5-HT binds to the extracellular N-terminus of the 5-HT(3A) receptor subunit, but receptor activation is also enhanced by distinct allosteric sites. It is not known if specific molecular subunits of the 5-HT(3) receptor modulate anxiety. To address this issue, we characterized anxiety-like behavior of mice with a targeted deletion of the 5-HT(3A) receptor subunit gene in the light/dark box, elevated plus maze, and novelty interaction animal models of anxiety. 5-HT(3A) null mice exhibited an anxiolytic behavioral phenotype that was highly correlated across behavioral measures. This evidence indicates that the 5-HT(3A) molecular subunit influences anxiety-like behavior. Pharmacotherapy that targets specifically the 5-HT(3A) receptor subunit may provide a novel treatment for anxiety disorders." [Abstract]

Morales, Marisela, Bloom, Floyd E.
The 5-HT3 Receptor Is Present in Different Subpopulations of GABAergic Neurons in the Rat Telencephalon
J. Neurosci. 1997 17: 3157-3167
""To analyze further the role of the 5-HT3R in the CNS, we used in situ hybridization and immunocytochemistry to determine that 5-HT3R-expressing neurons are mainly GABA-containing cells in the rat telencephalon. We determined that 5-HT3R/GABA-containing neurons do not exhibit somatostatin immunoreactivity but often contain cholecystokinin (CCK) immunoreactivity. 5-HT3R-expressing cells with CCK immunoreactivity were observed in the neocortex, olfactory cortex, hippocampus, and amygdala. The 5-HT3R/CCK interneurons represent between 35 and 66% of the total population of CCK-containing cells in the neocortex." [Full Text]

Paudice, P, Raiteri, M
Cholecystokinin release mediated by 5-HT3 receptors in rat cerebral cortex and nucleus accumbens
Br. J. Pharmacol. 1991 103: 1790-1794
"It is concluded that 5-HT can act as a potent releaser of CCK-LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5-HT3 type situated on the CCK-releasing terminals. This interaction may provide a rationale for the clinical development of both 5-HT3 and CCK receptor antagonists as novel anxiolytic drugs." [Article]

Koyama, Susumu, Matsumoto, Nozomu, Kubo, Chiharu, Akaike, Norio
Presynaptic 5-HT3 receptor-mediated modulation of synaptic GABA release in the mechanically dissociated rat amygdala neurons
J Physiol (Lond) 2000 529: 373-383
"Our results suggest that a 5-HT3-specific agonist acts on presynaptic nerve terminals facilitating synaptic GABA release without postsynaptic effects. The facilitation requires calcium influx through presynaptic 5-HT3 receptors. PKA modulates the recovery process from desensitization of presynaptic 5-HT3 receptor-mediated regulation of synaptic GABA release." [Full Text]

Hasegawa M, Sasaki T, Sadakane K, Tabuchi M, Takeda Y, Kimura M, Fujii Y.
Studies for the emetic mechanisms of ipecac syrup (TJN-119) and its active components in ferrets: involvement of 5-hydroxytryptamine receptors.
Jpn J Pharmacol 2002 Jun;89(2):113-9
"Ipecac syrup, prepared from a galentical ipecac, contains the nauseant alkaloids cephaeline and emetine. The involvement of receptors and serotonin- and dopamine-metabolizing enzymes in the emesis induced by ipecac syrup and these components was investigated. 1) In ferrets, the selective 5-HT3-receptor antagonist ondansetron (0.5 mg/kg, p.o.) prevented each emesis induced by TJN-119 (0.5 mL/kg, p.o.), cephaeline (0.5 mg/kg, p.o.) and emetine (5.0 mg/kg, p.o.), but the intraperitoneal administration of the selective dopamine D2-receptor antagonist sulpiride failed to significantly suppress the TJN-119, cephaeline and emetine-induced emesis at a dose of 0.1 mg/kg that blocked apomorphine-induced emesis. 2) In the receptor binding assays, cephaeline and emetine had a distinct affinity to 5-HT4 receptor, but no or weak affinity to 5-HT1A, 5-HT3, nicotine, M3, beta1, NK1, and D2 receptors. 3) Cephaeline and emetine did not affect activities of metabolic enzymes of 5-HT and dopamine (MAO-A, MAO-B, tryptophan 5-hydroxylase and tyrosine hydroxylase) in vitro. These results suggest that 5-HT3 receptor plays an important role in the emetic action of TJN-119, cephaeline and emetine, and the 5-HT4 receptor may be involved in their mechanisms." [Abstract]

Bedford, Fiona K., Julius, David, Ingraham, Holly A.
Neuronal Expression of the 5HT3 Serotonin Receptor Gene Requires Nuclear Factor 1 Complexes
J. Neurosci. 1998 18: 6186-6194
"We report here that the proximal TATA-less promoter of the serotonin-gated ion channel is sufficient for neuronal-specific expression in cultured cell lines. Moreover, an element within this 219 bp fragment matching the known consensus binding site for the NF1 family serves as an essential cis-regulatory element for this restricted transcriptional activity." [Full Text]

Peter Linz, and Roland Veelken
Serotonin 5-HT3 receptors on mechanosensitive neurons with cardiac afferents
Am J Physiol Heart Circ Physiol 282: H1828-H1835, May 2002. [Abstract]

Adrienne E. Dubin, Rene Huvar, Michael R. D'Andrea, Jayashree Pyati, Jessica Y. Zhu, K. C. Joy, Sandy J. Wilson, Jose E. Galindo, Charles A. Glass, Lin Luo, Michael R. Jackson, Timothy W. Lovenberg, and Mark G. Erlander
The Pharmacological and Functional Characteristics of the Serotonin 5-HT3A Receptor Are Specifically Modified by a 5-HT3B Receptor Subunit
J. Biol. Chem. 274: 30799-30810, October 1999.
"We report the cloning of a subunit 5-HT3B with ~44% amino acid identity to 5-HT3A that specifically modified 5-HT3A receptor kinetics, voltage dependence, and pharmacology. Co-expression of 5-HT3B with 5-HT3A modified the duration of 5-HT3 receptor agonist-induced responses, linearized the current-voltage relationship, increased agonist and antagonist affinity, and reduced cooperativity between subunits. Reverse transcriptase-polymerase chain reaction in situ hybridization revealed co-localization of both 5-HT3B and 5-HT3A in a population of neurons in the amygdala, telencephalon, and entorhinal cortex. Furthermore, 5-HT3A and 5-HT3B mRNAs were expressed in spleen and intestine. Our data suggest that 5-HT3B might contribute to tissue-specific functional changes in 5-HT3-mediated signaling and/or modulation." [Full Text]

Gunthorpe, Martin J., Peters, John A., Gill, Catherine H., Lambert, Jeremy J., Lummis, Sarah C. R.
The 4'lysine in the putative channel lining domain affects desensitization but not the single-channel conductance of recombinant homomeric 5-HT3A receptors
J Physiol (Lond) 2000 522: 187-198
"The 5-HT3 receptor is a transmitter-gated ion channel of the Cys-loop superfamily. Uniquely, 5-HT3 receptor subunits (5-HT3A and 5-HT3B) possess a positively charged lysine residue within the putative channel lining M2 domain (4' position). Using whole cell recording techniques, we examined the role of this residue in receptor function using wild-type (WT) and mutant 5-HT3A receptor subunits of murine origin transiently expressed in human embryonic kidney (HEK 293) cells." [Full Text]

Brown, A. M., Hope, A. G., Lambert, J. J., Peters, J. A.
Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A)
J Physiol (Lond) 1998 507: 653-665
"The data indicate that homo-oligomeric receptors composed of h5-HT3A subunits form inwardly rectifying cation-selective ion channels of low conductance that are permeable to Ca2+ and Mg2+." [Full Text]

David C. Reeves, Eric N. Goren, Myles H. Akabas, and Sarah C. R. Lummis
Structural and Electrostatic Properties of the 5-HT3 Receptor Pore Revealed by Substituted Cysteine Accessibility Mutagenesis
J. Biol. Chem. 276: 42035-42042.
"The 5-HT31 receptor is a member of the Cys loop family of ligand-gated ion channels, which includes nicotinic acetylcholine (nACh), GABAA and glycine receptors. These receptors are pentamers, usually formed by the co-assembly of one to four different subunits each with a large extracellular N-terminal region and four putative transmembrane domains (M1-M4)." [Full Text]

Tim Green, Kathrin A. Stauffer, and Sarah C. R. Lummis
Expression of Recombinant Homo-oligomeric 5-Hydroxytryptamine Receptors Provides New Insights into Their Maturation and Structure
J. Biol. Chem. 270: 6056-6061, March 1995. [Full Text]

Martin J. Gunthorpe, and Sarah C. R. Lummis
Conversion of the Ion Selectivity of the 5-HT3A Receptor from Cationic to Anionic Reveals a Conserved Feature of the Ligand-gated Ion Channel Superfamily
J. Biol. Chem. 276: 10977-10983, April 2001.
"The results presented here show that the introduction of three point mutations in or near the M2 domain are sufficient to convert the ion selectivity of homomeric 5-HT3A receptors from cationic to anionic. Substitution of V13'T in M2 together with the neutralization of a ring of glutamate residues (E1'A) and the adjacent insertion of the "extra" amino acid (proline) found in the anionic channels (referred to here as P1") in the M1-M2 loop (Fig. 1) lead to the formation of an anion-selective 5-HT3A receptor." [Full Text]

Lobitz, Nicole, Gisselmann, Gunter, Hatt, Hanns, Wetzel, Christian H.
A Single Amino-Acid in the TM1 Domain Is an Important Determinant of the Desensitization Kinetics of Recombinant Human and Guinea Pig {alpha}-Homomeric 5-Hydroxytryptamine Type 3 Receptors
Mol Pharmacol 2001 59: 844-851 [Full Text]

Dong Yan, Marvin K. Schulte, Karen E. Bloom, and Michael M. White
Structural Features of the Ligand-binding Domain of the Serotonin 5HT3 Receptor
J. Biol. Chem. 274: 5537-5541, February 1999.
"The data presented here are consistent with the notion that there is a significant amount of structural and functional homology between the AChR and 5HT3R (and by inference, the other members of the ligand-gated ion channel family)." [Full Text]

Coultrap, Steven J., Sun, Hongwei, Tenner, Thomas E., Jr., Machu, Tina K.
Competitive Antagonism of the Mouse 5-Hydroxytryptamine3 Receptor by Bisindolylmaleimide I, a "Selective" Protein Kinase C Inhibitor
J Pharmacol Exp Ther 1999 290: 76-82 [Full Text]

Machu, Tina K., Hamilton, Margaret E., Frye, Tonia F., Shanklin, Christopher L., Harris, Michael C., Sun, Hongwei, Tenner, Thomas E., Jr., Soti, Ferenc S., Kem, William R.
Benzylidene Analogs of Anabaseine Display Partial Agonist and Antagonist Properties at the Mouse 5-Hydroxytryptamine3A Receptor
J Pharmacol Exp Ther 2001 299: 1112-1119 [Abstract]

Khan, Naim Akhtar, Hichami, Aziz
Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells.
BIOCHEMICAL JOURNAL , 344(1):199-204 1999 [Abstract]

Wang, Yun, Ramage, Andrew G., Jordan, David
Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal preganglionic neurones in anaesthetized rats
J Physiol (Lond) 1998 509: 683-694 [Full Text]

Moore, Kimberly A., Taylor, Glen E., Weinreich, Daniel
Serotonin unmasks functional NK-2 receptors in vagal sensory neurones of the guinea-pig
J Physiol (Lond) 1999 514: 111-124
"In sum, these results suggest that stimulation of 5-HT3 receptors activates an intracellular signalling cascade that couples calcium-calmodulin and NO activation to NK-2 receptor unmasking in sensory neurones." [Full Text]

Fu, Liang-Wu, Longhurst, John C.
Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats
J Physiol (Lond) 1998 509: 729-740
"Data from the present study strongly suggest that 5-HT produced during ischaemia contributes to activation of ischaemically sensitive abdominal sympathetic C fibre afferents through stimulation of 5-HT3 receptors." [Full Text]

De Deurwaerdere, Philippe, Stinus, Luis, Spampinato, Umberto
Opposite Change of In Vivo Dopamine Release in the Rat Nucleus Accumbens and Striatum That Follows Electrical Stimulation of Dorsal Raphe Nucleus: Role of 5-HT3 Receptors
J. Neurosci. 1998 18: 6528-6538 [Full Text]

Herges, Sonja, Taylor, David A.
Involvement of 5-HT3 receptors in the nucleus accumbens in the potentiation of cocaine-induced behaviours in the rat
Br. J. Pharmacol. 2000 131: 1294-1302 [Abstract]

Roerig, Birgit, Nelson, Darin A., Katz, Lawrence C.
Fast Synaptic Signaling by Nicotinic Acetylcholine and Serotonin 5-HT3 Receptors in Developing Visual Cortex
J. Neurosci. 1997 17: 8353-8362
"Thus, both acetylcholine and serotonin can mediate fast synaptic transmission in the visual cortex; the early onset of these mechanisms suggests a role during initial stages of circuit formation and during subsequent experience-dependent remodeling of cortical connections." [Full Text]

Roerig, Birgit, Katz, Lawrence C.
Modulation of Intrinsic Circuits by Serotonin 5-HT3 Receptors in Developing Ferret Visual Cortex
J. Neurosci. 1997 17: 8324-8338 [Full Text]

Johannes A. van Hooft, Avron D. Spier, Jerrel L. Yakel, Sarah C. R. Lummis, and Henk P. M. Vijverberg
Promiscuous coassembly of serotonin 5-HT3 and nicotinic (alpha)4 receptor subunits into Ca2+-permeable ion channels
PNAS 95: 11456-11461, September 1998
"The results demonstrate that 5-HT3R and nAChR (alpha)4 subunits coassemble into a novel type of heteromeric 5-HT3 receptor channel with enhanced Ca2+ permeability and reduced sensitivity to the antagonist d-tubocurarine as compared with the homomeric 5-HT3 receptor-gated ion channel. These findings have significant implications, both for 5-HT3R pharmacology and function and for ligand-gated ion channels in general." [Full Text]

Steve Kriegler, Sterling Sudweeks, and Jerrel L. Yakel
The Nicotinic (alpha)4 Receptor Subunit Contributes to the Lining of the Ion Channel Pore When Expressed with the 5-HT3 Receptor Subunit
J. Biol. Chem. 274: 3934-3936, February 1999.
"Our demonstration that the nicotinic (alpha)4 subunit lines the pore of the channel is consistent with the idea that it could modify the single channel conductance and calcium permeability of the 5-HT3R. This may be a general strategy used in neurons to produce the wide range of properties reported." [Full Text]

Zhai, Jin, Gershon, Michael D., Walsh, John H., Wong, Helen C., Kirchgessner, Annette L.
Inward Currents in Neurons from Newborn Guinea Pig Intestine: Mediation by 5-Hydroxytryptamine Type 3 Receptors
J Pharmacol Exp Ther 1999 291: 374-382 [Full Text]

X. W. Fu, D. Wang, J. Pan, S. M. Farragher, V. Wong, and E. Cutz
Neuroepithelial bodies in mammalian lung express functional serotonin type 3 receptor
Am J Physiol Lung Cell Mol Physiol 281: L931-L940, October 2001.
"Our studies suggest that 5-HT3-R in NEB cells may function as an autoreceptor and may potentially be involved in modulation of hypoxia signaling." [Abstract]

Zeitz, Karla P., Guy, Nicolas, Malmberg, Annika B., Dirajlal, Sahera, Martin, William J., Sun, Linda, Bonhaus, Douglas W., Stucky, Cheryl L., Julius, David, Basbaum, Allan I.
The 5-HT3 Subtype of Serotonin Receptor Contributes to Nociceptive Processing via a Novel Subset of Myelinated and Unmyelinated Nociceptors
J. Neurosci. 2002 22: 1010-1019
"Serotonin is a major component of the inflammatory chemical milieu and contributes to the pain of tissue injury via an action on multiple receptor subtypes. Here we studied mice after genetic or pharmacological disruption of the 5-HT3 receptor, an excitatory serotonin-gated ion channel. We demonstrate that tissue injury-induced persistent, but not acute, nociception is significantly reduced after functional elimination of this receptor subtype. Specifically, in the setting of tissue injury, the 5-HT3 receptor mediates activation of nociceptors but does not contribute to injury-associated edema. This result is explained by the localization of 5-HT3 receptor transcripts to a previously uncharacterized subset of myelinated and unmyelinated afferents, few of which express the proinflammatory neuropeptide substance P. Finally, we provide evidence that central serotonergic circuits modulate nociceptive transmission via a facilitatory action at spinal 5-HT3 receptors. We conclude that activation of both peripheral and central 5-HT3 receptors is pronociceptive and that the contribution of peripheral 5-HT3 receptors involves a novel complement of primary afferent nociceptors."
[Abstract]

Ferezou, Isabelle, Cauli, Bruno, Hill, Elisa L., Rossier, Jean, Hamel, Edith, Lambolez, Bertrand
5-HT3 Receptors Mediate Serotonergic Fast Synaptic Excitation of Neocortical Vasoactive Intestinal Peptide/Cholecystokinin Interneurons
J. Neurosci. 2002 22: 7389-7397 [Abstract]

Wolf H.
Preclinical and clinical pharmacology of the 5-HT3 receptor antagonists.
Scand J Rheumatol Suppl 2000;113:37-45
"5-HT3-receptor antagonists are potent and highly selective competitive inhibitors of the 5-HT3-receptor with negligible affinity for other receptors. They are rapidly absorbed and penetrate the blood-brain barrier easily. 5-HT3-receptor antagonists are metabolized by diverse subtypes of the cytochrome P450-system, metabolites are excreted mainly in urine. Half-lifes in healthy subjects vary from 3-4 hours (ondansetron, granisetron) to 7-10 hours (tropisetron, hydrodolasetron). 5-HT3-receptor antagonists do not modify any aspect of normal behaviour in animals or induce remarkable changes of physiological functions in healthy subjects. They are well tolerated over wide dose ranges, most common side effects in clinical use are headache and obstipation. Clinical efficacy was first established in chemotherapy-induced emesis. In this indication, 5-HT3-receptor antagonists set a new standard regarding efficacy and tolerability. Further established indications are radiotherapy-induced and post-operative emesis. Antiemetic efficacy results from a simultaneous action at peripheral and central 5-HT3-receptors. Other peripheral actions include reduction of secretion and diarrhea caused by increased intestinal serotonin content (e.g. in carcinoid syndrome), a limited antiarrhythmic activity and a reduction of experimentally induced pain. CNS effects comprise anxiolysis, attenuation of age-associated memory impairment, reduction of alcohol consumption in moderate alcohol abuse and an antipsychotic effect in patients with parkinson psychosis. In migraine, 5-HT3-receptor antagonists show moderate efficacy, as well. Repeatedly demonstrated efficacy of 5-HT3-receptor antagonists in patients suffering from fibromyalgia raises the question for the mechanism of action involved. Ligand binding at the 5-HT3-receptor causes manifold effects on other neurotransmitter and neuropeptide systems. In particular, 5-HT3-receptor antagonists diminish serotonin-induced release of substance P from C-fibers and prevent unmasking of NK2-receptors in the presence of serotonin. These observations possibly provide an approach for the causal explanation of favourable treatment results with 5-HT3-receptor antagonists in fibromyalgia." [Abstract]

Stratz T, Muller W.
The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechanism of action of these agents in fibromyalgia?
Scand J Rheumatol Suppl 2000;113:66-71
"With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron." [Abstract]

Sirota, Pinkhas, Mosheva, Tanya, Shabtay, Hertzel, Giladi, Nir, Korczyn, Amos D.
Use of the Selective Serotonin 3 Receptor Antagonist Ondansetron in the Treatment of Neuroleptic-Induced Tardive Dyskinesia
Am J Psychiatry 2000 157: 287-289 [Abstract]

Christian H. R. Wetzel, Bettina Hermann, Christian Behl, Elmar Pestel, Gerhard Rammes, Walter Zieglgänsberger, Florian Holsboer, and Rainer Rupprecht
Functional Antagonism of Gonadal Steroids at the 5-Hydroxytryptamine Type 3 Receptor
Mol. Endocrinol. 12: 1441-1451, 1998.
"The functional antagonism of gonadal steroids at the 5-HT3 receptor may play a role for the development and course of nausea during pregnancy and of psychiatric disorders." [Full Text]

Stratz T, Schochat T, Hrycaj P, Lacki J, Mennet P, Farber L, Schweiger C, Muller W.
[Therapy of generalized tendomyopathy (fibromyalgia) caused by blocking 5-HT3 receptors]
Z Rheumatol 1994 Nov-Dec;53(6):335-8
"In more than 40% of patients with fibromyalgia a marked influence on the pain in the skeletal system with a decrease of the tenderness at "tenderpoints" can be achieved by blocking the 5-HT3-receptors with ondansetron or tropisetron-hydrochloride. Physical complaints and vegetative signs also improve. It is discussed if patients not responding to therapy with ondansetron or tropisetron-hydrochloride have to be discriminated as a subgroup of fibromyalgia." [Abstract]

Farber L, Stratz TH, Bruckle W, Spath M, Pongratz D, Lautenschlager J, Kotter I, Zoller B, Peter HH, Neeck G, Welzel D, Muller W
Short-term treatment of primary fibromyalgia with the 5-HT3-receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients.
Int J Clin Pharmacol Res 2001;21(1):1-13
"Short-term treatment of fibromyalgia patients with 5 mg tropisetron for 10 days proved to be efficacious and well tolerated. In this study a bell-shaped dose-response curve was seen." [Abstract]

Samborski W, Stratz T, Lacki JK, Klama K, Mennet P, Muller W.
The 5-HT3 blockers in the treatment of the primary fibromyalgia syndrome: a 10-day open study with Tropisetron at a low dose.
Mater Med Pol 1996 Jan-Mar;28(1):17-9
"The efficacy of Tropisetron in a dose of 5 mg daily was comparable with the results obtained in a previously reported trial with a dose of 10 or 15 mg per day, but the frequency of gastric troubles decreased (21% vs. 60%)." [Abstract]

Muller W, Stratz T.
Results of the intravenous administration of tropisetron in fibromyalgia patients.
Scand J Rheumatol Suppl 2000;113:59-62
"The observed effects on the symptoms of fibromyalgia of daily oral administration of 5 mg of the 5-HT3 receptor antagonist, tropisetron, for 10 days, could be maintained or exceeded with intravenous administration of only 2 mg of the formulation. Following a single i.v. injection of 2 mg tropisetron, a more rapid and profound reduction in pain was achieved than with 5 mg oral tropisetron per day. In individual cases, patients who had previously experienced no reduction in pain from 10 days of 5 mg oral tropisetron daily responded to i.v. therapy. A more favourable and persistent effect on pain, combined with a simultaneous significant improvement in various vegetative and functional symptoms was achieved with five days treatment with 2 mg tropisetron i.v. per day." [Abstract]

Haus U, Varga B, Stratz T, Spath M, Muller W.
Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.
Scand J Rheumatol Suppl 2000;113:55-8
"In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment." [Abstract]

Rodd-Henricks ZA, McKinzie DL, Melendez RI, Berry N, Murphy JM, McBride WJ.
Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats.
Psychopharmacology (Berl) 2002 Nov 23
"RATIONALE. Previous work from our laboratory indicated that Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA) and that 5-HT(3) antagonists will inhibit EtOH-stimulated somatodendritic release of dopamine within the VTA.OBJECTIVES. The objective of this study was to use the intracranial self-administration procedure to determine the involvement of 5-HT(3)receptors in mediating the reinforcing effects of EtOH within the VTA, and to increase our understanding of central nervous system mechanisms involved in the rewarding effects of EtOH.METHODS. Adult female Wistar rats were stereotaxically implanted with guide cannulae aimed at the posterior VTA. After 1 week, rats were placed into standard two-lever experimental chambers for a total of seven sessions (4-h sessions separated by 48 h) and allowed to self-administer vehicle alone, a 5-HT(3) antagonist alone, 200 mg% EtOH alone, or combinations of 200 mg% EtOH with different concentrations of a 5-HT(3) antagonist ( n=6-9 per group).RESULTS. Throughout all seven sessions, Wistar rats self-infused more 200 mg% ETOH (25+/-5 infusions) than vehicle (5+/-4 infusions) or 5-HT(3) antagonist (6+/-4 infusions) ( P<0.05), and responded significantly more ( P<0.05) on the active than inactive lever (e.g., 50+/-12 vs 12+/-8 responses in session 1). Co-administration of 50 micro M or 100 micro M ICS 205,930 with 200 mg% EtOH completely prevented the acquisition and maintenance of EtOH self-infusion into the posterior VTA. Similarly, co-administration of either 25-100 micro M LY-278-584 or 10-100 micro M zacopride with 200 mg% EtOH completely blocked EtOH-maintained intracranial self-administration behavior.CONCLUSIONS. The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT(3) receptors." [Abstract]

Panicker, Sandip, Cruz, Hans, Arrabit, Christine, Slesinger, Paul A.
Evidence for a Centrally Located Gate in the Pore of a Serotonin-Gated Ion Channel
J. Neurosci. 2002 22: 1629-1639 [Abstract]

Mott, David D., Erreger, Kevin, Banke, Tue G., Traynelis, Stephen F.
Open probability of homomeric murine 5-HT3A serotonin receptors depends on subunit occupancy
J Physiol (Lond) 2001 535: 427-443 [Full Text]

Hanna, Michael C., Davies, Paul A., Hales, Tim G., Kirkness, Ewen F.
Evidence for Expression of Heteromeric Serotonin 5-HT3 Receptors in Rodents.
J Neurochem 2000 75: 240-247 [Abstract]

Steward, Lucinda J., Boess, Frank G., Steele, Joy A., Liu, Dan, Wong, Norris, Martin, Ian L.
Importance of Phenylalanine 107 in Agonist Recognition by the 5-Hydroxytryptamine3A Receptor
Mol Pharmacol 2000 57: 1249-1255 [Full Text]

Hope, Anthony G., Belelli, Delia, Mair, Ian D., Lambert, Jeremy J., Peters, John A.
Molecular Determinants of (+)-Tubocurarine Binding at Recombinant 5-Hydroxytryptamine3A Receptor Subunits
Mol Pharmacol 1999 55: 1037-1043
"Interestingly, several of the residues exerting a subtle effect upon the apparent affinity of ACh are homologous to amino acids within mouse and human 5-HT3A subunits that contribute to the differential potency of (+)-Tc." [Full Text]

Lankiewicz, Silke, Lobitz, Nicole, Wetzel, Christian H. R., Rupprecht, Rainer, Gisselmann, Gunter, Hatt, Hanns
Molecular Cloning, Functional Expression, and Pharmacological Characterization of 5-Hydroxytryptamine3 Receptor cDNA and Its Splice Variants from Guinea Pig
Mol Pharmacol 1998 53: 202-212 [Full Text]

Zhou, Xiaoping, Galligan, James J.
Synaptic Activation and Properties of 5-Hydroxytryptamine3 Receptors in Myenteric Neurons of Guinea Pig Intestine
J Pharmacol Exp Ther 1999 290: 803-810 [Full Text]

Steward, Lucinda J., Boess, Frank G., Steele, Joy A., Liu, Dan, Wong, Norris, Martin, Ian L.
Importance of Phenylalanine 107 in Agonist Recognition by the 5-Hydroxytryptamine3A Receptor
Mol Pharmacol 2000 57: 1249-1255 [Full Text]

PAUL A. DAVIES, MARCO PISTIS†, MICHAEL C. HANNA, JOHN A. PETERS, JEREMY J. LAMBERT, TIM G. HALES & EWEN F. KIRKNESS
The 5-HT3B subunit is a major determinant of serotonin-receptor function
Nature 397, 359 - 363 (1999)
"In addition to providing a new target for therapeutic agents, the 5-HT3B subunit will be a valuable resource for defining the molecular mechanisms of ion-channel function." [Abstract]

Avron D. Spier, and Sarah C. R. Lummis
The Role of Tryptophan Residues in the 5-Hydroxytryptamine3 Receptor Ligand Binding Domain
J. Biol. Chem. 275: 5620-5625, February 2000. [Full Text]

Kawa, K.
Distribution and functional properties of 5-HT3 receptors in the rat hippocampal dentate gyrus: a patch-clamp study
J Neurophysiol 1994 71: 1935-1947 [Abstract/Full Text]

Dang, Hong, England, Pamela M., Farivar, S. Sarah, Dougherty, Dennis A., Lester, Henry A.
Probing the Role of a Conserved M1 Proline Residue in 5-Hydroxytryptamine3 Receptor Gating
Mol Pharmacol 2000 57: 1114-1122 [Full Text]

Charlotte M. Deane, and Sarah C. R. Lummis
The Role and Predicted Propensity of Conserved Proline Residues in the 5-HT3 Receptor
J. Biol. Chem. 276: 37962-37966, October 2001. [Full Text]

Sun, Hongwei, McCardy, Elizabeth A., Machu, Tina K., Blanton, Michael P.
Characterization of Interaction of 3,4,5-Trimethoxybenzoic Acid 8-(Diethylamino)octyl Ester with Torpedo californica Nicotinic Acetylcholine Receptor and 5-Hydroxytryptamine3 Receptor
J Pharmacol Exp Ther 1999 290: 129-135 [Full Text]

Ye, Jiang Hong, Schaefer, Rebecca, Wu, Wen-Hsien, Liu, Philip L., Zbuzek, Vlasta K., Mcardle, Joseph J.
Inhibitory Effect of Ondansetron on Glycine Response of Dissociated Rat Hippocampal Neurons
J Pharmacol Exp Ther 1999 290: 104-111
"When examined under current clamp conditions, glycine induced depolarization and hyperpolarization in neonatal and mature neurons, respectively; ondansetron also suppressed these responses to glycine. The data suggest that ondansetron competitively inhibits the glycine receptor." [Full Text]

McMahon, Lori L., Kauer, Julie A.
Hippocampal Interneurons Are Excited Via Serotonin-Gated Ion Channels
J Neurophysiol 1997 78: 2493-2502
"We have demonstrated that CA1 SR interneurons are excited by 5-HT via direct activation of postsynaptic 5-HT3 receptors. The 5-HT responses persist during blockade of fast glutamatergic and GABAergic synaptic transmission, indicating that 5-HT receptors are present on interneurons themselves. The responses are independent of G-protein activation and are effectively blocked by three distinct 5-HT3 receptor antagonists." [Full Text]

Harris LC, Awe SO, Opere CA, LeDay AM, Ohia SE, Sharif NA.
Pharmacology of serotonin receptors modulating electrically-induced [3h]-norepinephrine release from isolated mammalian iris-ciliary bodies.
J Ocul Pharmacol Ther 2002 Aug;18(4):339-48
"We conclude that the excitatory prejunctional 5-HT heteroreceptors present in bovine iris-ciliary bodies belong to the 5-HT3 receptor subtype." [Abstract]

Rosenberg, Madelaine, Pie, Brigitte, Cooper, Ellis
Developing Neonatal Rat Sympathetic and Sensory Neurons Differ in Their Regulation of 5-HT3 Receptor Expression
J. Neurosci. 1997 17: 6629-6638 [Full Text]

Smith, George M., Berry, Richard L., Yang, Jay, Tanelian, Darrell
Electrophysiological Analysis of Dorsal Root Ganglion Neurons Pre- and Post-Coexpression of Green Fluorescent Protein and Functional 5-HT3 Receptor
J Neurophysiol 1997 77: 3115-3121 [Full Text]