 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C16H23N5O |
| Molecular Weight | 301.39 |
| Exact Mass | 301.19 |
| Elemental Analysis | C, 63.76; H, 7.69; N, 23.24; O, 5.31 |
| CAS # | 145158-71-0 |
| Related CAS # | Tegaserod maleate;189188-57-6 |
| PubChem CID | 135409453 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 470.6±48.0 °C at 760 mmHg |
| Melting Point | 180-183ºC |
| Flash Point | 238.4±29.6 °C |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C |
| Index of Refraction | 1.597 |
| LogP | 2.91 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 22 |
| Complexity | 385 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CCCCCN=C(N)N/N=C/C1=CNC2=C1C=C(C=C2)OC |
| InChi Key | IKBKZGMPCYNSLU-RGVLZGJSSA-N |
| InChi Code | InChI=1S/C16H23N5O/c1-3-4-5-8-18-16(17)21-20-11-12-10-19-15-7-6-13(22-2)9-14(12)15/h6-7,9-11,19H,3-5,8H2,1-2H3,(H3,17,18,21)/b20-11+ |
| Chemical Name | 1-[(E)-(5-methoxy-1H-indol-3-yl)methylideneamino]-2-pentylguanidine |
| Synonyms | Tegaserod maleate; CPD000471618; 189188-57-6; DTXSID50904761; HMS2051J10 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | 5-HT4 Receptor |
| ln Vitro |
Tegaserod (3-5 μM; 24-72 hours) significantly increases apoptosis in a time- and dose-dependent manner [1]. Tegaserod (TM) exerts its anti-cancer effects independently of serotonin signaling. Tegaserod (TM) blunts of ribosomal protein S6 (S6) phosphorylation through the PI3K/Akt/mTOR pathway[1].
Tegaserod lowers p-S6 and p-p70 S6 (Thr421/Ser424)[1] at 3-5 μM over 8–18 hours. According to 5-HT2B receptor antagonist activity, tegaserod (0.1-3 μM; 24 hours) efficiently suppresses 5-HT-mediated contraction of the rat gastric fundus in vitro (pA2=8.3) [3].
1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 receptor agonist activity. 2 Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi=7.5, 8.4 and 7.0, respectively). The 5-HT2B receptor-binding affinity of tegaserod was identical to that at human recombinant 5-HT4(c) receptors (mean pKi=8.4) in human embryonic kidney-293 (HEK-293) cells stably transfected with the human 5-HT4(c) receptor. 3 Tegaserod (0.1-3 microm) inhibited 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA2=8.3), consistent with 5-HT(2B) receptor antagonist activity. Tegaserod produced, with similar potency, an elevation of adenosine 3',5' cyclic monophosphate in HEK-293 cells stably transfected with the human 5-HT4(c) receptor (mean pEC50=8.6), as well as 5-HT4) receptor-mediated relaxation of the rat isolated oesophagus (mean pEC50=8.2) and contraction of the guinea-pig isolated colon (mean pEC50=8.3).[3] |
| ln Vivo |
Tegaserod (5 mg/kg/day; intraperitoneal injection; five days in a row) inhibits p-S6 in vivo, decreases metastasis, and delays the formation of tumors [1]. Tegaserod (0.1-2.0 mg/kg; i.p. 15 min before gastric loading) dramatically increases the rate at which gastric glucose is emptied from the stomach in db/db mice and maintains it at 0.1 mg/kg for 30 minutes. This results in an 80% reduction in the amount of food consumed[2].
Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. Conclusions: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis. [2] Following subcutaneous administration, Tegaserod (0.3 or 1 mg kg(-1)) inhibited contractions of the stomach fundus in anaesthetized rats in response to intravenous dosing of alpha-methyl 5-HT (0.03 mg kg(-1)) and BW 723C86 (0.3 mg kg(-1)), selective 5-HT2B receptor agonists. At similar doses, tegaserod (1 and 3 mg kg(-1) subcutaneously) evoked a 5-HT4 receptor-mediated increase in colonic transit in conscious guinea-pigs. 5 The data from this study indicate that tegaserod antagonizes 5-HT2B receptors at concentrations similar to those that activate 5-HT4 receptors. It remains to be determined whether this 5-HT2B receptor antagonist activity of tegaserod contributes to its clinical profile.[3] Tegaserod (TM) delays tumor growth, reduces metastases, increases survival and suppresses p-S6 in vivo. [1] To evaluate the efficacy of TM against melanoma tumor growth we used a syngeneic immune-competent model. Mice were subcutaneously inoculated with B16F10 cells, and 7 days later, randomized and treated with daily injections of TM or vehicle for 5 days. Treatment significantly decreased tumor growth (Fig. 4a) and resulted in only slight decreases in weight following treatment (Additional file 1: Figure S6A). There were no changes in liver damage markers AST, LDH and ALT (Additional file 1: Figure S6B). The in vitro TM-mediated PI3K/Akt/mTOR signaling inhibition was re-capitulated in vivo. When immunohistochemical staining of tumor tissue harvested 13 days post inoculation was performed for phosphorylation of S6 (Ser235/236), one third of control tumor slides were classified as having a high positive score. This is sharp contrast to tumors from TM treated mice where only one slide scored as having a high positive score (Fig. 4b). Images were scored for positive staining using the IHC profiler which employs an automated, unbiased approach to evaluate antibody staining in tissue sections. Furthermore, tumor lysates from TM treated mice had significantly lower Akt and S6 phosphorylation levels (Fig. 4c)[1]. |
| Enzyme Assay |
Binding assay conditions [3] Human recombinant 5-HT2A, 5-HT2B, 5-HT2C and 5-HT4(c) receptor membrane radioligand-binding assays were conducted as described previously (Grossman et al., 1993; Stam et al., 1994; Bonhaus et al., 1995; Pindon et al., 2002). Briefly, membranes prepared from cells stably transfected with human recombinant 5-HT2A, 5-HT2B, 5-HT2C and 5-HT4(c) receptors were incubated with radiolabelled ligands with a high affinity for the given receptor, that is, [3H]ketanserin, [N-methyl-3H]lysergic acid diethylamide (LSD), [3H]mesulergine and [3H]GR113808, respectively. Nonspecific radioligand binding was defined by ketanserin (1 μM), 5-HT (10 μM), SB 242084 (10 μM) and GR113808 (1 μM), respectively. Competition-binding studies were conducted with increasing concentrations of unlabelled ligand (10 pM–30 μM) and a fixed concentration of radioligand (in nM): [3H]ketanserin (0.5), [N-methyl-3H]LSD (1.2), [3H]mesulergine and [3H]GR113808 (0.15). For [3H]GR113808, the radioligand concentration was ∼6-fold the KD value, but for all others the concentration was at, or close to, the KD. Following an incubation period sufficient to reach equilibrium: 15 min at 37°C, 30 min at 37°C, 30 min at 37°C and 60 min at 22°C, respectively, the membranes were harvested by rapid filtration and bound radioactivity quantitated by liquid scintillation spectroscopy. Binding data were analysed by nonlinear regression analysis using GraphPad Prism™ software and a three-parameter model for one-site competition. pKi (negative decadic logarithm of Ki) values for test compounds were calculated from the best-fit IC50 values, and the Kd value of the radioligand, using the Cheng–Prusoff equation (Cheng & Prusoff, 1973): Ki=IC50/(1+[L]/Kd), where [L] is the concentration of the radioligand. |
| Cell Assay |
Apoptosis Analysis[1] Cell Types: A375, RPMI-7951 (RPMI), SH4, B16F10, MeWo and MEL-JUSO Tested Concentrations: 3, 5 μM Incubation Duration: 24, 48, 72 h Experimental Results: There was a significant time and dose-dependent increase in apoptosis in all cell lines. Western Blot Analysis[1] Cell Types: RPMI, SH4 and B16F10 cells Tested Concentrations: 3, 5 μM Incubation Duration: 8 or 18 h Experimental Results: diminished phosphorylation of the kinase directly upstream of S6, p70 S6 at Thr421/Ser424. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 J mice were subcutaneously (sc) injected with B16F10 cells[1] Doses: 5 mg/ kg Route of Administration: Administered intraperitoneally (ip) (ip) daily for five days Experimental Results: Treatment Dramatically diminished tumor growth and resulted in only slight decreases in weight following treatment. Animal/Disease Models: Female C57BLKS/J db/db mice[2] Doses: 0.1, 0.5 , 1.0, 2.0 mg/kg Route of Administration: IP 15 min prior to gastric loading Experimental Results: Produced a dramatic decrease in the fraction of the meal remaining in the stomach for doses as low as 0.1 mg/kg (0.1 mg/kg). Accelerated gastric emptying, with a reduction of nearly 80% in the fraction remaining at 30 min (P < 0.0001) (0.1 mg/kg). Induced a significant decrease in the gastric emptying rate as the amount of the meal remaining at 30 min was Dramatically greater (2.0 mg/kg). Resulted in inhibition of tegaserod-induced increased gastric emptying (0.1 mg/kg). C57BL/6 J mice were maintained under specific pathogen-free conditions. Seven to nine week old C57BL/6 J mice were subcutaneously injected with 5 × 105 B16F10 cells. Seven days post injection, when tumor volume reached approximately 50 mm3, mice were randomized and treated daily for 5 consecutive days with 5 mg/kg tegaserod or vehicle control (2.5% DMSO in PBS). Tegaserod and vehicle were administered intraperitoneally (i.p.). Tumors were measured using calipers and tumor volume was calculated using the following formula: (tumor length x width2)/2. For metastases quantification experiments, C57BL/6 J mice were intravenously injected with 2 × 105 B16F10 cells and treatment with Tegaserod and vehicle (administered i.p.) occurred 1 day post inoculation and continued three times weekly till day 14 post inoculation at which time mice were sacrificed. Metastases from lungs, stored in PBS for short term storage, were manually counted. For survival experiments, C57BL/6 J mice were intravenously injected with 105 B16F10 cells. Treatment with Tegaserod and vehicle (administered i.p.) occurred 1 day post inoculation and continued three times weekly till day 17 post inoculation. [1] Gastric emptying rates of the glucose solution in control and diabetic mice were determined first. Mice were sacrificed 5, 10, 20, 30 and 40 min after the meal was instilled into the stomach. Four mice per data point were used. Serum glucose levels were checked using an Accu-chek III test reader (Roche Diagnostics Corporation, Indianapolis, IN, USA) with a drop of blood obtained by sectioning the tip of the tail of the animal. The effect of tegaserod on gastric emptying was evaluated in diabetic mice. Tegaserod was given via an intraperitoneal (i.p.) injection 15 min prior to gastric loading at a dose of 0.1, 0.5, 1.0 or 2.0 mg kg−1. Mice were sacrificed 30 min after meal administration. Four db/db mice per dose of tegaserod were used. The effects of tegaserod were compared with those obtained after i.p. administration of vehicle (mixture of DMSO and saline). In four mice, the effects of 5HT4 receptor blockade on tegaserod mediated effects were evaluated by administering GR11308, a 5HT4 antagonist (3.0 mg kg−1, i.p.) 10 min before tegaserod injection. Drug preparation Tegaserod was used. Injectable solutions of GR11308, a 5HT-4 antagonist, and tegaserod were prepared after solubilization in 1-methyl 2-pyrrolidinone. The solutions were diluted with normal saline to obtain final concentrations of tegaserod ranging from 0.01 to 0.2 mg ml−1, and a final concentration of GR11308 of 0.3 mg ml−1. For both compounds, the injectable volume was exactly 0.1 mL per 10 g of animal.[2] Rats were allowed at least 30 min to stabilize following surgery. Typically, spontaneous rhythmical changes in balloon pressure commenced during this period, representing contractility of the stomach fundus. The selective 5-HT2B receptor agonists, α-methyl 5-HT (0.03 mg kg−1) and BW 723C86 (0.3 mg kg−1), or their vehicles, were administered via the jugular venous catheter (1 ml kg−1). These doses of α-methyl 5-HT and BW 723C86 were selected, as in initial experiments they were associated with increases in stomach pressure without marked changes in blood pressure. At 15 min after dosing with α-methyl 5-HT (0.03 mg kg−1), tegaserod or its vehicle was administered subcutaneously (1 ml kg−1). The selective 5-HT4 receptor antagonist, piboserod (1 mg kg−1; Sanger et al., 1998), was co-administered with tegaserod to exclude any influence of 5-HT4 receptor activation on stomach pressure. After a further 15 min, rats were dosed with α-methyl 5-HT (0.03 mg kg−1). Responses to α-methyl 5-HT were compared, by measuring the amplitude and area of stomach contractions, and data were expressed for the second α-methyl 5-HT challenge as a percentage of the first (statistical significance at P<0.05 by ANOVA and Dunnett's post hoc test, comparing the tegaserod and vehicle-induced responses). To avoid tachyphylaxis, each rat was challenged only once with BW 723C86, 15 min after subcutaneous co-administration of piboserod (1 mg kg−1) with either tegaserod (1 mg kg−1) or its vehicle, and data were compared by unpaired Student's t-test, with statistical significance set at P<0.05. The effect of the selective 5-HT2B/2C receptor antagonist, SB 206553 (1 mg kg−1; Kennett et al., 1996), on the BW 723C86 responses was also investigated. [3] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion The absolute bioavailability of tegaserod is approximately 10% when administered to fasting subjects. The median time of peak tegaserod plasma concentration (Tmax) is approximately one hour (range 0.7 to 2 hours). Nevertheless, when tegaserod was given to individuals thirty minutes before a meal of high-fat and high-calorie content (about 150 calories from protein, 250 calories from carbohydrates, and 500 calories from fat), the AUC was reduced by 40% to 65%, the Cmax was reduced by approximately 20% to 40%, and the median Tmax was 0.7 hours. Additionally, plasma concentrations were similar when tegaserod was administered within thirty minutes before a meal or even two and a half hours after a meal. Approximately two-thirds of an orally administered dose of tegaserod is excreted unchanged in the feces, with the remaining one-third excreted in the urine as metabolites. Although tegaserod is not approved for intravenous administration, data regarding the mean volume of distribution of tegaserod at steady-state is recorded as 368 ± 223 L following research of tegaserod administered intravenously. Although tegaserod is not approved for intravenous administration, data regarding the mean plasma clearance of tegaserod is documented as 77 ± 15 L/h following research of tegaserod administered intravenously. Metabolism / Metabolites Tegaserod is ultimately metabolized by way of hydrolysis and direct glucuronidation. The substance is firstly hydrolyzed in the stomach. It then undergoes oxidization and then conjugation to produce the main circulating tegaserod metabolite in human plasma, the so-called M29 metabolite, or 5-methoxyindole-3-carboxylic acid. Nevertheless, it has been determined that this main circulating metabolite has negligible affinity for 5-HT(4) receptors in vitro. Furthermore, tegaserod can also experience direct N-glucuronidation at each of its three guanidine nitrogens which leads to the generation of three isomeric N-glucuronides - the so-called M43.2, M43.8, and M45.3 metabolites. Tegaserod has known human metabolites that include 1-[(E)-(5-Hydroxy-1H-indol-3-yl)methylideneamino]-2-pentylguanidine. Biological Half-Life The mean terminal elimination half-life documented for tegaserod ranges from 4.6 to 8.1 hours following oral administration. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of tegaserod during breastfeeding. Because of the potential for serious adverse reactions in the breastfed infant, an alternate drug is preferred. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding The protein binding recorded for tegaserod is about 98%. |
| References |
[1]. Repurposing the serotonin agonist Tegaserod as an anticancer agent in melanoma: molecular mechanisms and clinical implications. J Exp Clin Cancer Res. 2020 Feb 21;39(1):38. [2]. The effects of tegaserod, a 5-HT receptor agonist, on gastric emptying in a murine model of diabetes mellitus. Neurogastroenterol Motil. 2005 Oct;17(5):738-43. [3]. The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol. 2004 Nov;143(5):549-60. |
| Additional Infomation |
Pharmacodynamics In general, it has been determined that tegaserod is an agonist of serotonin type-4 (5-HT(4)) receptors, an antagonist at 5-HT(2B) receptors, but is expected to possess minimal binding to 5-HT(1) receptors, and virtually no affinity for 5-HT(3) or dopamine receptors. In clinical trials with tegaserod, centrally analyzed ECGs were recorded in 4,605 male and female patients receiving tegaserod 6 mg twice daily or placebo for IBS-C and other related motility disorders. No subject receiving the agent had an absolute QTcF above 480 ms. An increase in QTcF of 30 to 60 ms was observed in 7% of patients receiving tegaserod and 8% receiving placebo. An increase in QTcF of greater than 60 ms was observed in 0.3% and 0.2% of subjects, respectively. The effects of tegaserod on the QTcF interval were ultimately not considered to be clinically meaningful. Furthermore, it was determined that there is a potential for tegaserod and its main metabolite (the M29 metabolite) to increase platelet aggregation in vitro. In one in vitro study, at concentrations up to 10-times the maximum plasma concentration (Cmax) at the recommended dose, tegaserod significantly increased platelet aggregation in a concentration-dependent manner up to 74% (range 11% to 74%) compared to a control vehicle (with potentiation by various agonists). In another in vitro study, the M29 metabolite, at concentrations up to 0.6-times the Cmax of M29 also showed a 5% to 16% increase in platelet aggregation compared to the control vehicle. The clinical implications of these in vitro platelet aggregation results remain unclear. Background: New therapies are urgently needed in melanoma particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors. Methods: Drug screening, IC50 determinations as well as synergy assays were detected by the MTT assay. Apoptosis using Annexin V and 7AAD staining was assessed using flow cytometry. TUNEL staining was performed using immunocytochemistry. Changes in phosphorylation of key molecules in PI3K/Akt/mTOR and other relevant pathways were detected by western blot as well as immunocytochemistry. To assess in vivo anti-tumor activity of Tegaserod, syngeneic intravenous and subcutaneous melanoma xenografts were used. Immunocytochemical staining was performed to detect expression of active Caspase-3, cleaved Caspase 8 and p-S6 in tumors. Evaluation of immune infiltrates was carried out by flow cytometry. Results: Using a screen of 770 pharmacologically active and/or FDA approved drugs, we identified Tegaserod (Zelnorm, Zelmac) as a compound with novel anti-cancer activity which induced apoptosis in murine and human malignant melanoma cell lines. Tegaserod (TM) is a serotonin receptor 4 agonist (HTR4) used in the treatment of irritable bowel syndrome (IBS). TM's anti-melanoma apoptosis-inducing effects were uncoupled from serotonin signaling and attributed to PI3K/Akt/mTOR signaling inhibition. Specifically, TM blunted S6 phosphorylation in both BRAFV600E and BRAF wildtype (WT) melanoma cell lines. TM decreased tumor growth and metastases as well as increased survival in an in vivo syngeneic immune-competent model. In vivo, TM also caused tumor cell apoptosis, blunted PI3K/Akt/mTOR signaling and decreased S6 phosphorylation. Furthermore TM decreased the infiltration of immune suppressive regulatory CD4+CD25+ T cells and FOXP3 and ROR-γt positive CD4+ T cells. Importantly, TM synergized with Vemurafenib, the standard of care drug used in patients with late stage disease harboring the BRAFV600E mutation and could be additively or synergistically combined with Cobimetinib in both BRAFV600E and BRAF WT melanoma cell lines in inducing anti-cancer effects. Conclusion: Taken together, we have identified a drug with anti-melanoma activity in vitro and in vivo that has the potential to be combined with the standard of care agent Vemurafenib and Cobimetinib in both BRAFV600E and BRAF WT melanoma.[1] The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5-HT(4) receptor partial agonist, on gastric emptying. Methods: Gastric emptying rates of a 20% glucose test meal were determined in 12-20-week-old female db/db mice and control littermates. The effects of tegaserod (0.1-2.0 mg kg(-1), i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5-HT(4)antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying. Results: Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. Conclusions: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.[2] 1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 receptor agonist activity. 2 Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi=7.5, 8.4 and 7.0, respectively). The 5-HT2B receptor-binding affinity of tegaserod was identical to that at human recombinant 5-HT4(c) receptors (mean pKi=8.4) in human embryonic kidney-293 (HEK-293) cells stably transfected with the human 5-HT4(c) receptor. 3 Tegaserod (0.1-3 microm) inhibited 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA2=8.3), consistent with 5-HT(2B) receptor antagonist activity. Tegaserod produced, with similar potency, an elevation of adenosine 3',5' cyclic monophosphate in HEK-293 cells stably transfected with the human 5-HT4(c) receptor (mean pEC50=8.6), as well as 5-HT4) receptor-mediated relaxation of the rat isolated oesophagus (mean pEC50=8.2) and contraction of the guinea-pig isolated colon (mean pEC50=8.3). 4 Following subcutaneous administration, tegaserod (0.3 or 1 mg kg(-1)) inhibited contractions of the stomach fundus in anaesthetized rats in response to intravenous dosing of alpha-methyl 5-HT (0.03 mg kg(-1)) and BW 723C86 (0.3 mg kg(-1)), selective 5-HT2B receptor agonists. At similar doses, tegaserod (1 and 3 mg kg(-1) subcutaneously) evoked a 5-HT4 receptor-mediated increase in colonic transit in conscious guinea-pigs. 5 The data from this study indicate that tegaserod antagonizes 5-HT2B receptors at concentrations similar to those that activate 5-HT4 receptors. It remains to be determined whether this 5-HT2B receptor antagonist activity of tegaserod contributes to its clinical profile.[3] |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~165.90 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (16.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (16.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (16.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3180 mL | 16.5898 mL | 33.1796 mL | |
| 5 mM | 0.6636 mL | 3.3180 mL | 6.6359 mL | |
| 10 mM | 0.3318 mL | 1.6590 mL | 3.3180 mL |