RESERPINE ASCORBATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H40N2O9.C6H8O6
Molecular Weight	784.8028
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(OC(=O)C(O)=C1O)[C@@H](O)CO.[H][C@]23C[C@@H](OC(=O)C4=CC(OC)=C(OC)C(OC)=C4)[C@H](OC)[C@@H](C(=O)OC)[C@@]2([H])C[C@@]5([H])N(CCC6=C5NC7=C6C=CC(OC)=C7)C3

InChI

InChIKey=WNJQGGIUASELQW-YDTMYOOKSA-N

InChI=1S/C33H40N2O9.C6H8O6/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;7-1-2(8)5-3(9)4(10)6(11)12-5/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3;2,5,7-10H,1H2/t18-,22+,24-,27-,28+,31+;2-,5+/m10/s1

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a4d74d7-2e63-4789-b50e-af17ced92462 | https://www.ncbi.nlm.nih.gov/pubmed/15529229 | https://www.ncbi.nlm.nih.gov/pubmed/23831411

Reserpine is an alkaloid, isolated from the Rauwolfia serpentina plant and developed by Ciba pharma. Reserpine was approved by FDA for the treatment of hypertension and psychotic disorders. The drug exerts its effect by blocking two vesicular monoamine transporters, VMAT1 and VMAT2. The blockade results in vesicles that lose their ability to store neurotransmitter molecules. Neurotransmitters, thus retained in cytosol, are then neutralized by MAO.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vesicular amine transporter 1 6 Target ID: CHEMBL1838 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23831411	Blocker 537		160.0 nM [IC50]
Synaptic vesicular amine transporter 57 Target ID: CHEMBL1893 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23831411	Blocker 537		350.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a4d74d7-2e63-4789-b50e-af17ced92462	Primary		Approved 8429	RESERPINE Approved Use Mild essential hypertension; also useful as adjunctive therapy with other antihypertensive agents in the more severe forms of hypertension; relief of symptoms in agitated psychotic states (e.g., schizophrenia), primarily in those individuals unable to tolerate phenothiazine derivatives or in those who also require antihypertensive medication. Launch Date 1955
Agitated psychotic states 6 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a4d74d7-2e63-4789-b50e-af17ced92462	Palliative		Approved 8429	RESERPINE Approved Use Mild essential hypertension; also useful as adjunctive therapy with other antihypertensive agents in the more severe forms of hypertension; relief of symptoms in agitated psychotic states (e.g., schizophrenia), primarily in those individuals unable to tolerate phenothiazine derivatives or in those who also require antihypertensive medication. Launch Date 1955

C_max

Value	Dose	Co-administered	Analyte	Population
0.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30465727	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		RESERPINE plasma	Equus caballus population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
4.8 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30465727	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		RESERPINE plasma	Equus caballus population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
23.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30465727	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		RESERPINE plasma	Equus caballus population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	Disc. AE: Drowsiness, Light headedness... AEs leading to discontinuation/dose reduction: Drowsiness (1 patient) Light headedness (light, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/17628352
0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	Disc. AE: Upper abdominal pain, Postural hypotension... AEs leading to discontinuation/dose reduction: Upper abdominal pain (1 patient) Postural hypotension (1 patient) Electrocardiogram abnormal (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/17628352

AEs

AE	Significance	Dose	Population
Drowsiness	1 patient Disc. AE	0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352
Light headedness	light, 1 patient Disc. AE	0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352
Electrocardiogram abnormal	1 patient Disc. AE	0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352
Postural hypotension	1 patient Disc. AE	0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352
Upper abdominal pain	1 patient Disc. AE	0.25 mg 2 times / day multiple, oral Dose: 0.25 mg, 2 times / day Route: oral Route: multiple Dose: 0.25 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17628352	unhealthy, 41.2 years n = 60 Health Status: unhealthy Condition: cocaine dependence Age Group: 41.2 years Sex: M+F Population Size: 60 Sources: https://pubmed.ncbi.nlm.nih.gov/17628352

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 activator 80	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BSEP 402 BCRP 699 MRP2 383 OATP1B1 788 OATP1B3 706 OATP2B1 123 CYP1A2 1524 CYP2C19 1478 CYP2A6 707 CYP2E1 882 Kv1.3 17 MRP3 157 MRP4 204	P-gp 1537	P-gp 257 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	activator 214 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzcyIn19	no [Activation >3.9811 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc3MiJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc3MiJ9fQ%3D%3D	no [IC50 >10 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24396142/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24396142/	no
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	unlikely [Inhibition 20 uM]
MRP3 207	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	weak [IC50 133 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	weak [IC50 133 uM]
Kv1.3 32	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0041008X11000706	weak [IC50 58 uM]
BSEP 403	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/reserpine/, https://pubmed.ncbi.nlm.nih.gov/19520776/	yes [IC50 2.8 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11743742/, https://pubmed.ncbi.nlm.nih.gov/24396142/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzcyIn19	yes [IC50 20.4 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31571164/, https://pubmed.ncbi.nlm.nih.gov/17430633/, http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50017712, https://pubmed.ncbi.nlm.nih.gov/23956101/	yes [IC50 26.3 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24396142/	yes [IC50 <0.03 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24396142/	yes [IC50 <0.2 uM]
OATP1B1 803	inhibitor 3277 Sources: https://go.drugbank.com/drugs/DB00206, https://pubmed.ncbi.nlm.nih.gov/22541068/	yes [Inhibition 20 uM]
OATP2B1 126	inhibitor 3277 Sources: https://go.drugbank.com/drugs/DB00206, https://pubmed.ncbi.nlm.nih.gov/22541068/	yes [Inhibition 20 uM]
P-gp 1650	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000050555, https://pubmed.ncbi.nlm.nih.gov/10080959/, http://transportal.compbio.ucsf.edu/compounds/reserpine/, https://pubmed.ncbi.nlm.nih.gov/12134945/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc3MiJ9fQ%3D%3D	yes [Ki 1.38 uM]
MRP2 475	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/reserpine/,https://go.drugbank.com/drugs/DB00206, https://pubmed.ncbi.nlm.nih.gov/12134946/, https://pubmed.ncbi.nlm.nih.gov/23956101/, https://www.genome.jp/kegg/drug/br08309.html, https://pubmed.ncbi.nlm.nih.gov/18457386/	yes [Ki 295 uM]
CYP3A4/5 335	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000050555, https://pubmed.ncbi.nlm.nih.gov/8632764/	yes
P-gp 1650	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000050555, https://pubmed.ncbi.nlm.nih.gov/8632764/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31571164/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.sciencedirect.com/science/article/pii/S0041008X11000706

PubMed

Title	Date	PubMed
The effect of 5-hydroxytrytamine synthesis inhibitors on neuroleptic-induced catalepsy in rats.	1975	1172422
Pharmacological analysis of a new anorexic substance: 5-hydroxy-5(4'-chlorophenyl)-2, 3-dihydro-5H-imidazo-(2, 1-a) isoindole (Mazindol).	1975 Apr	1171662
[Behavior pharmacology of maprotiline, a new antidepressant].	1975 Nov	1240830
Transient global amnesia associated with cardiac arrhythmia and digitalis intoxication.	1975 Sep-Oct	1179459
On the anticataleptic action of cyproheptadine.	1976 Aug	1033567
Antidepressant effect of an ethanolic extract of the leaves of Cissampelos sympodialis in rats and mice.	1998 Dec	10030729
Reserpine modulates serotonin transporter mRNA levels in the rat brain.	1999	10027743
The adrenergic receptor agonist, clonidine, potentiates the anti-parkinsonian action of the selective kappa-opioid receptor agonist, enadoline, in the monoamine-depleted rat.	1999 Dec	10602339
Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.	2001 Apr	11264240
Spectrophotometric, septrofluorimetric and LC determination of lisinopril.	2001 Jul	11377074
Striatal cannabinoid CB1 receptor mRNA expression is decreased in the reserpine-treated rat model of Parkinson's disease.	2001 Jun	11358453
Application of conventional UV, photodiode array (PDA) and fluorescence (FL) detection to analysis of phenolic acids in plant material and pharmaceutical preparations.	2001 Mar	11248502
Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats.	2001 May	11318962
A simple, isocratic high-performance liquid chromatography assay for linezolid in human serum.	2001 Nov	11679548
Determination of aliphatic amines in water by liquid chromatography using solid-phase extraction cartridges for preconcentration and derivatization.	2001 Oct	11693606
[Determination of nitidine in different parts of Zanthoxylum nitidum].	2001 Sep	11799776
Rapid high-performance liquid chromatographic method for the separation of hydroxylated testosterone metabolites.	2001 Sep 5	11530987
High-performance liquid chromatographic, capillary electrophoretic and capillary electrophoretic-electrospray ionisation mass spectrometric analysis of selected alkaloid groups.	2002 Aug 16	12219932
[Determination of ofloxacin in human fallopian tube, uterus and serum by high performance liquid chromatography].	2002 Feb	12579960
Increase of free cysteine and citric acid in plant cells exposed to cobalt ions.	2002 Jul	12052512
Validated HPLC method for determination of sennosides A and B in senna tablets.	2002 Jul 31	12093522
Determination of undecylenic and sorbic acids in cosmetic preparations by high performance liquid chromatography with electrochemical detection.	2002 Nov 7	12408884
Interaction of cytochrome P450 3A inhibitors with P-glycoprotein.	2002 Oct	12235267
Development and substantiation of a liquid chromatographic method for monitoring organic reactions involved in synthesis of 4-methoxyphenylacetic acid.	2002 Oct 4	12416886
Analysis of flecainide and two metabolites in biological specimens by HPLC: application to a fatal intoxication.	2003 Jan-Feb	12587684
Assessment of a controlled release hydrophilic matrix formulation for metoclopramide HCl.	2003 May	12754009
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.	2003 May 21	12748199

Patents

Sample Use Guides

In Vivo Use Guide

Hypertension: In the average patient not receiving other antihypertensive agents, the usual initial dosage is 0.5 mg daily for 1 or 2 weeks. For maintenance, reduce to 0.1-0.25 mg daily. Psychiatric Disorders: the usual initial dosage is 0.5 mg daily, but may range from 0.1 mg to 1.0 mg. Adjust dosage upward or downward according to the patient's response.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

RESERPINE ASCORBATE

Common Name

English

3.BETA.,20.ALPHA.-YOHIMBAN-16.BETA.-CARBOXYLIC ACID, 18.BETA.-HYDROXY-11,17.ALPHA.-DIMETHOXY- METHYL ESTER 3,4,5-TRIMETHOXYBENZOATE (ESTER), L-ASCORBATE

Systematic Name

English

YOHIMBAN-16-CARBOXYLIC ACID, 11,17-DIMETHOXY-18-((3,4,5-TRIMETHOXYBENZOYL)OXY)-, METHYL ESTER, (3.BETA.,16.BETA.,17.ALPHA.,18.BETA.,20.ALPHA.)-, MONO-L-ASCORBATE

Systematic Name

English

RESERPINE, ASCORBATE

Common Name

English

L-ASCORBIC ACID, COMPD. WITH METHYL 18.BETA.-HYDROXY-11,17.ALPHA.-DIMETHOXY-3.BETA.,20.ALPHA.-YOHIMBAN-16.BETA.-CARBOXYLATE 3,4,5-TRIMETHOXYBENZOATE (ESTER)

Common Name

English

Code System Code Type Description

PUBCHEM

92135773

Created by admin on Sat Dec 16 10:14:48 GMT 2023 , Edited by admin on Sat Dec 16 10:14:48 GMT 2023

PRIMARY

CAS

20235-11-4

Created by admin on Sat Dec 16 10:14:48 GMT 2023 , Edited by admin on Sat Dec 16 10:14:48 GMT 2023

NON-SPECIFIC STOICHIOMETRY

FDA UNII

D632O8555Z

Created by admin on Sat Dec 16 10:14:48 GMT 2023 , Edited by admin on Sat Dec 16 10:14:48 GMT 2023

PRIMARY

ACTIVE MOIETY


					8B1QWR724A

RESERPINE

SUBSTANCE RECORD


					D632O8555Z

RESERPINE ASCORBATE

Details

SMILES

InChI

DescriptionSources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a4d74d7-2e63-4789-b50e-af17ced92462 | https://www.ncbi.nlm.nih.gov/pubmed/15529229 | https://www.ncbi.nlm.nih.gov/pubmed/23831411

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a4d74d7-2e63-4789-b50e-af17ced92462 | https://www.ncbi.nlm.nih.gov/pubmed/15529229 | https://www.ncbi.nlm.nih.gov/pubmed/23831411

C_max

T_1/2

Drug as perpetrator