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Prucalopride (R 108512; R108512; R 108512; trade names: Resolor; Resotran; Motegrity), a novel enterokinetic and benzofuran-based compound, is a novel, selective, high affinity 5-HT (serotonin) receptor agonist for 5-HT4A and 5-HT4B receptor with anti-idiopathic constipation activity. It shows >290-fold selectivity for 5-HT4A and 5-HT4B over other 5-HT receptor subtypes and inhibits 5-HT4A and 5-HT4B with Ki values of 2.5 nM and 8 nM, respectively. With a pEC50 of 7.5, prucalopride causes contractions in a concentration-dependent manner. Following electrical field stimulation, prucalopride dramatically increases the guinea pig proximal colon's rebound contraction. The FDA approved prucalopride in December 2018 for the treatment of idiopathic chronic constipation.
Physicochemical Properties
| Molecular Formula | C22H32CLN3O7 | |
| Molecular Weight | 485.96 | |
| Exact Mass | 485.192 | |
| Elemental Analysis | C, 54.38; H, 6.64; Cl, 7.29; N, 8.65; O, 23.05 | |
| CAS # | 179474-85-2 | |
| Related CAS # | Prucalopride; 179474-81-8 | |
| PubChem CID | 9870009 | |
| Appearance | White to off-white solid powder | |
| LogP | 3.117 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 9 | |
| Rotatable Bond Count | 9 | |
| Heavy Atom Count | 33 | |
| Complexity | 538 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | ClC1=C(C2C([H])([H])C([H])([H])OC=2C(=C1[H])C(N([H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])OC([H])([H])[H])C([H])([H])C1([H])[H])=O)N([H])[H].O([H])C(C([H])([H])C([H])([H])C(=O)O[H])=O |
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| InChi Key | QZRSNVSQLGRAID-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C18H26ClN3O3.C4H6O4/c1-24-9-2-6-22-7-3-12(4-8-22)21-18(23)14-11-15(19)16(20)13-5-10-25-17(13)14;5-3(6)1-2-4(7)8/h11-12H,2-10,20H2,1H3,(H,21,23);1-2H2,(H,5,6)(H,7,8) | |
| Chemical Name | 4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide;butanedioic acid | |
| Synonyms |
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| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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-HT4A Receptor ( pKi = 8.6 ); 5-HT4B Receptor ( pKi = 8.1 ) | |
| ln Vitro |
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| ln Vivo |
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| Animal Protocol | In the prefrontal cortex, prucalopride maximally increased ACh and histamine levels at 5 and 10 mg/kg, while PRX-03140 significantly increased cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses below 150 mg/kg, according to studies using microdialysis in rats. | |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No published experience exists with prucalopride during breastfeeding. However, the manufacturer reports an unpublished study that indicates a relatively low amount of drug in breastmilk. Until more data become available, monitor the breastfed infant for diarrhea. ◉ 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. |
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| References |
[1]. Eur J Pharmacol . 2001 Jun 29;423(1):71-83. [2]. Neuropharmacology . 2012 Apr;62(5-6):2126-35. [3]. Eur J Pharmacol . 2013 Apr 5;705(1-3):156-63. [4]. Neurogastroenterol Motil . 2001 Oct;13(5):465-72. |
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| Additional Infomation |
Prucalopride Succinate is the succinate salt form of prucalopride, an orally bioavailable dihydro-benzofuran-carboxamide and selective serotonin (5-HT4) receptor agonist, with gastrointestinal (GI) prokinetic activity. Upon oral administration, prucalopride specifically targets, binds to and stimulates the 5-HT4 receptor. This alters colonic motility patterns and stimulates colonic mass movements. This may normalize bowel movements and may relief chronic constipation. In addition, by increasing esophageal and gastric motility, prucalopride may also provide relief for aspiration-associated symptoms. See also: Prucalopride (has active moiety). Drug Indication Resolor is indicated for symptomatic treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief. Treatment of chronic constipation, Treatment of opioid-induced constipation |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.14 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 25.0 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: ≥ 2.5 mg/mL (5.14 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 25.0 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: ≥ 2.5 mg/mL (5.14 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 25.0 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 | 2.0578 mL | 10.2889 mL | 20.5778 mL | |
| 5 mM | 0.4116 mL | 2.0578 mL | 4.1156 mL | |
| 10 mM | 0.2058 mL | 1.0289 mL | 2.0578 mL |