methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8-tetraene-19-carboxylate

• ChemBase ID: 91
• Molecular Formular: C33H40N2O9
• Molecular Mass: 608.6787
• Monoisotopic Mass: 608.27338087
• SMILES: O([C@@H]1[C@H]([C@@H]2[C@@H](CN3[C@H](C2)c2[nH]c4c(c2CC3)ccc(OC)c4)C[C@H]1OC(=O)c1cc(OC)c(OC)c(OC)c1)C(=O)OC)C
• Canonical SMILES: COc1ccc2c(c1)[nH]c1c2CCN2[C@@H]1C[C@H]1[C@@H](C2)C[C@H]([C@@H]([C@H]1C(=O)OC)OC)OC(=O)c1cc(OC)c(c(c1)OC)OC
• InChI: InChI=1S/C33H40N2O9/c1-38-19-7-8-20-21-9-10-35-16-18-13-27(44-32(36)17-11-25(39-2)30(41-4)26(12-17)40-3)31(42-5)28(33(37)43-6)22(18)15-24(35)29(21)34-23(20)14-19/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3/t18-,22+,24-,27-,28+,31+/m1/s1
• InChIKey: QEVHRUUCFGRFIF-MDEJGZGSSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.0^2,^1^0.0^4,^9.0^1^5,^2^0]henicosa-2(10),4,6,8-tetraene-19-carboxylate; methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.0^{2,10}.0^{4,9}.0^{15,20}]henicosa-2(10),4,6,8-tetraene-19-carboxylate
• IUPAC Traditional name: unipres; methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.0^2,^1^0.0^4,^9.0^1^5,^2^0]henicosa-2(10),4,6,8-tetraene-19-carboxylate; methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.0^{2,10}.0^{4,9}.0^{15,20}]henicosa-2(10),4,6,8-tetraene-19-carboxylate
• Brand Name: Cam-Ap-Es; Demi-Regroton; Diupres-250; Diupres-500; Diutensen-R; Dralserp; Hiserpia; Hydrap-ES; Hydromox R; Hydroserpine Plus (R-H-H); Metatensin #2; Metatensin #4; Naquival; Novoreserpine; Rau-Sed; Regroton; Renese-R; Reserfia; Salutensin; Salutensin-Demi; Sandril; Ser-A-Gen; Serpalan; Serpanray; Serpasil; Serpasil-Apresoline; Serpasil-Esidrix #1; Serpasil-Esidrix #2; Serpate; Serpivite; Unipres
• Synonyms: Reserpine; (1S,2R,3R,4aS,13bR,14aS)-methyl 2,11-dimethoxy-3-((3,4,5-trimethoxybenzoyl)oxy)-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate; (3β,16β,17α,18β,20α)-11,17-Dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic Acid Methyl Ester; 3,4,5-Trimethoxybenzoyl Methyl Reserpate; Anquil; Apoplon; Rivasin; Serpasil; Temposerpine; Triserpin; Sermix; Reserpoid; Sandril; Carpacil; Reserpine; Reserpine Standard for LC-MS; 利血平; 利血平; LC-MS 利血平标准溶液

Database IDs

• CAS Number: 50-55-5
• EC Number: 200-047-9
• MDL Number: MFCD00005091
• Beilstein Number: 102014
• PubChem SID: 160963554; 24888118; 24278208; 46505863
• PubChem CID: 5770
• CHEBI ID: 28487
• ATC CODE: C02AA02
• CHEMBL: 772
• Chemspider ID: 5566
• DrugBank ID: DB00206
• KEGG ID: D00197
• Unique Ingredient Identifier: 8B1QWR724A
• Wikipedia Title: Reserpine
• Medline Plus: a601107

CALCULATED PROPERTIES

JChem

• Acid pKa: 16.290113
• H Acceptors: 8
• H Donor: 1
• LogD (pH = 5.5): 1.7332709
• LogD (pH = 7.4): 3.2777264
• Log P: 3.531496
• Molar Refractivity: 161.4185 cm^3
• Polarizability: 64.298744 Å^3
• Polar Surface Area: 117.78 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.05
• LOG S: -4.73
• Solubility (Water): 1.13e-02 g/l

PROPERTIES

Physical Property

• Solubility: 73 mg/L; Chloroform; Methanol (hot)
• Apperance: Off-White to Pale Yellow Solid
• Melting Point: ~265 °C (dec.); >220°C (dec.)
• Flash Point: 22 °C; 71.6 °F
• Optical Rotation: [α]20/D -123±3°, c = 1% in chloroform
• Hydrophobicity(logP): 3.2

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Warning: Hygroscopic
• RTECS: ZG0350000
• European Hazard Symbols: Irritant (Xi); Harmful (Xn)
• UN Number: 1219
• German water hazard class: 1; 3
• Hazard Class: 3
• Packing Group: 2
• Risk Statements: 10-36-67; 22
• Safety Statements: 22-36/37/39; 26
• GHS Pictograms: GHS02; GHS07
• GHS Signal Word: Danger; Warning
• GHS Hazard statements: H225-H319-H336; H302
• GHS Precautionary statements: P210-P261-P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves; Eyeshields, Faceshields, full-face respirator (US), Gloves, multi-purpose combination respirator cartridge (US), type ABEK (EN14387) respirator filter
• RID/ADR: UN 1219 3/PG 2
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: oral
• Bioavailability: 50%
• Excretion: 62% feces / 8% urine
• Half Life: phase 1 = 4.5h,; phase 2 = 271h, ; average = 33h
• Metabolism: gut/liver
• Legal Status: Rx-only (some countries banned/discontinued)
• Pregnancy Category: D (fetotoxic)
• US Licence: Reserpine
• Gene Information: human ... HTR1A(3350), HTR1B(3351), HTR1D(3352), HTR1E(3354), HTR1F(3355), HTR2A(3356), HTR2B(3357), HTR2C(3358), HTR3A(3359), HTR3B(9177), HTR3C(170572), HTR3D(200909), HTR3E(285242), HTR4(3360), HTR5A(3361), HTR5B(645694), HTR6(3362), HTR7(3363)
• Mechanism of Action: Disruption of norepinephrine, serotonin, and dopamine presynaptic vesicles by the transporter VMAT

Product Information

• Purity: ≥99.0% (HPLC)
• Concentration: 5 mg/L in water: isopropyl alcohol (1:1)
• Grade: analytical standard
• Salt Data: Free Base
• Suitability: corresponds for mass spectrometry
• Biological Source: Alkaloid from Rauwolfia serpentina, Rauwolfia vomitoria, Rauwolfia macrophylla , very many other Rauwolfia spp., Vinca minor, Alstonia constricta and many other spp. in the Apocynaceae, e.g. Tenduzia longifolia, Vallesia dichotoma and Excavatia coccinea
• Shelf Life: (limited shelf life, expiry date on the label)
• Application(s): Antiadrenergic; Anticonvulsant agent; Antihypertensive agent acting by depleting stores of noradrenaline in sympathetic neurones; Antineoplastic agent; Possesses sedative tranquilliser props.
• Quality: crystallized
• Empirical Formula (Hill Notation): C33H40N2O9

DETAILS

DrugBank - DB00206

• Drug Groups: approved
• Description: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [PubChem]
• Indication: Foe the treatment of hypertension
• Pharmacology: Reserpine is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance.
• Toxicity: Possible human carcinogen. May cause reproductive harm. ORL-RAT LD₅₀ 420 mg/kg; IPR-RAT LD₅₀ 44 mg/kg; IVN-RAT LD₅₀ 15 mg/kg; ORL-MUS LD₅₀ 200 mg/kg; SCU-MUS LD₅₀ 52 mg/kg; IPR-RBT LD₅₀ 7 mg/kg
• Affected Organisms: Humans and other mammals
• Protein Binding: 62%
• Elimination: Reserpine is extensively metabolized to inactive compounds. It is slowly excreted via the urine and feces.
• References: : Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1979 Dec 7;242(23):2562-71. [Pubmed] ; : Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967 Dec 11;202(11):1028-34. [Pubmed] ; : Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991 Jun 26;265(24):3255-64. [Pubmed] ; Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. Epub 2003 May 14. [Pubmed] ; Moser M: "Cost containment" in the management of hypertension. Ann Intern Med. 1987 Jul;107(1):107-9. [Pubmed]
• External Links: Wikipedia; Drugs.com

Selleck Chemicals - S1601

Research Area: Cardiovascular Disease
Biological Activity:
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today. Reserpine acts by blocking the vesicular monoamine transporter VMAT, which normally transports free norepinephrine, serotonin, and dopamine from the cytoplasm of the presynaptic nerve into vesicles for subsequent release into the synaptic cleft. The unprotected neurotransmitters are then metabolized by MAO and therefore never reach the synapse. [1]

Sigma Aldrich - R0875

Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
Biochem/physiol Actions
Inhibits vesicular uptake of catecholamines and serotonin.

Sigma Aldrich - 83580

Biochem/physiol Actions
Inhibits vesicular uptake of catecholamines and serotonin.

Sigma Aldrich - 43530

Biochem/physiol Actions
Inhibits vesicular uptake of catecholamines and serotonin.

Toronto Research Chemicals - R144600

An indole alkaloid found in Rauwolfia serpentina. Inhibits vesicular uptake of catecholamines and serotonin. Reserpine is reasonably anticipated to be a human carcinogen. Antihypertensive.

REFERENCES

• : Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1979 Dec 7;242(23):2562-71. Pubmed
• : Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967 Dec 11;202(11):1028-34. Pubmed
• : Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991 Jun 26;265(24):3255-64. Pubmed
• Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. Epub 2003 May 14. Pubmed
• Moser M: "Cost containment" in the management of hypertension. Ann Intern Med. 1987 Jul;107(1):107-9. Pubmed
• http://en.wikipedia.org/wiki/Reserpine
• Muller, J.M., et al.: Experientia, 8, 338 (1952)
• Schirmer, R.E., et al.: Anal. Profiles Drug Subs., 4, 384 (1952)
• Diener, R.M., et al.: Toxicol. Pathol., 8, 1 (1952)
• Aldrich Library of FT-IR Spectra, 1st edn., 1985, 2, 1069C, (ir)
• Aldrich Library of 13C and 1H FT NMR Spectra, 1992, 3, 615A, (nmr)
• Furlenmeyer, A. et al., Experientia, 1953, 9, 331, (uv, ir)
• Velluz, L. et al., Bull. Soc. Chim. Fr., 1958, 145; 673, (synth)
• Woodward, R.B. et al., Tetrahedron, 1958, 2, 1, (synth)
• Ban, Y. et al., Tetrahedron, 1964, 20, 2877, (config)
• Schlittler, E., Alkaloids (N.Y.), 1965, 8, 287, (rev)
• Levin, R.H. et al., J.O.C., 1973, 38, 1983, (cmr)
• Taylor, W.I. et al., The Vinca Alkaloids, Marcel Dekker, 1973, (rev, props)
• Becker, O. et al., Org. Mass Spectrom., 1977, 12, 461, (ms)
• Pearlman, B.A., J.A.C.S., 1979, 101, 6404, (synth)
• Bein, H.J., Handb. Exp. Pharmacol., (Part 1), 1980, 55, 43-58, (rev, pharmacol)
• IARC Monog., 1980, 24, 211; Suppl., 6, 485; Suppl., 7, 330, (rev, tox)
• Wender, P.A. et al., J.A.C.S., 1980, 102, 6157, (synth)
• Muhtadi, F.J., Anal. Profiles Drug Subst., 1984, 13, 737, (rev, ir, pmr, cmr, ms, anal)
• Lounasmaa, M. et al., Heterocycles, 1985, 23, 371, (pmr)
• Szntay, C. et al., Alkaloids (N.Y.), 1986, 27, 253, (pharmacol, bibl)
• Martin, S.F. et al., J.A.C.S., 1987, 109, 6124, (synth)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 6th edn., Akademie-Verlag, 1987, 7993, (synonyms)
• Stork, G., Pure Appl. Chem., 1989, 61, 439, (synth)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 343; 386
• Chu, C.S. et al., Chem. Comm., 1996, 1537, (synth)
• Nicolaou, K.C. et al., Classics in Total Synthesis, Targets, Strategies, Methods, VCH, 1996, 55, (bibl, synth)
• Hanessian, S. et al., J.O.C., 1997, 62, 465, (synth)
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, DIG800; DIH000; RDK000