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Details

Stereochemistry ABSOLUTE
Molecular Formula C33H40N2O9.ClH.H2O
Molecular Weight 663.155
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RESERPINE HYDROCHLORIDE MONOHYDRATE

SMILES

O.Cl.[H][C@]12C[C@@H](OC(=O)C3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]4([H])N(CCC5=C4NC6=C5C=CC(OC)=C6)C2

InChI

InChIKey=QHYQAXNPCCUMMY-IOSAXKQOSA-N
InChI=1S/C33H40N2O9.ClH.H2O/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;1H;1H2/t18-,22+,24-,27-,28+,31+;;/m1../s1

HIDE SMILES / InChI
Molecular Formula C33H40N2O9
Molecular Weight 608.6787
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Ciba-Geigy
88
Curator's Comment: Later Ciba-Geigy and now Novartis.

Approval Year

1954
117
Targets

Targets

Primary TargetPharmacologyConditionPotency
Blocker
537
 160.0 nM [IC50]
Blocker
537
 350.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
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
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587

activator
80
inhibitor
1767
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther 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​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1925
 no [Activation >3.9811 uM]
CYP2A6
739
 no [IC50 >10 uM]
CYP2E1
970
 no [IC50 >10 uM]
CYP1A2
1692
 no
CYP2C9
1819
 no
OATP1B3
715
 unlikely [Inhibition 20 uM]
MRP3
207
 weak [IC50 133 uM]
MRP4
238
 weak [IC50 133 uM]
Kv1.3
32
 weak [IC50 58 uM]
BSEP
403
 yes [IC50 2.8 uM]
CYP3A4
1925
 yes [IC50 20.4 uM]
BCRP
773
 yes [IC50 26.3 uM]
CYP2C19
1553
 yes [IC50 <0.03 uM]
CYP2D6
1891
 yes [IC50 <0.2 uM]
OATP1B1
803
 yes [Inhibition 20 uM]
OATP2B1
126
 yes [Inhibition 20 uM]
P-gp
1650
 yes [Ki 1.38 uM]
MRP2
475
 yes [Ki 295 uM]
CYP3A4/5
335
 yes
P-gp
1650
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
PubMed

PubMed

TitleDatePubMed
Effects of aminergic drugs and glutamic acid on audiogenic seizures induced by early exposure to ethanol.
1975 Mar
[Behavior pharmacology of maprotiline, a new antidepressant].
1975 Nov
[Characterization and recognition key components in Astragalus membranaceus].
2001 Jul
[Determination of intestinal trefoil factor in burned rats by reversed-phase high performance liquid chromatography].
2001 Jul
[Recognition and quantitative contrast characteristic components for root of Chinese angelica].
2001 Mar
[Determination of bifonazole in cream by high performance liquid chromatography].
2001 May
[Study of diphacinone in biological samples by high performance liquid chromatography/diode array detector].
2001 May
[Determination of acyclovir in mouse plasma and tissues by reversed-phase high performance liquid chromatography].
2001 Nov
Studies on the cardiotoxicity of noradrenaline in isolated rabbit hearts.
2002
Identification of mammary carcinogens in rodent bioassays.
2002
Behavioral effects of MK-801 on reserpine-treated mice.
2002 Apr
Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids.
2002 Apr
Augmentation of immune cell activity against tumor cells by Rauwolfia radix.
2002 Aug
High-performance liquid chromatographic, capillary electrophoretic and capillary electrophoretic-electrospray ionisation mass spectrometric analysis of selected alkaloid groups.
2002 Aug 16
[Determination of ofloxacin in human fallopian tube, uterus and serum by high performance liquid chromatography].
2002 Feb
Temperature effect on peak width and column efficiency in subcritical water chromatography.
2002 Feb
Nitecapone and selegiline as effective adjuncts to L-DOPA in reserpine-induced catatonia in mice.
2002 Jan-Feb
[Application of fingerprint chromatogram in quality control of Shen-Mai injection].
2002 Jul
Determination of L-sesamin and L-asarinin in Zanthoxylum(Roxb.) DC. by high performance liquid chromatography.
2002 Jul
Increase of free cysteine and citric acid in plant cells exposed to cobalt ions.
2002 Jul
Determination of terbutaline sulfate and its degradation products in pharmaceutical formulations using LC.
2002 Jul 31
Validated HPLC method for determination of sennosides A and B in senna tablets.
2002 Jul 31
Development and optimization of a reversed-phase high-performance liquid chromatographic method for the determination of piperacillin and tazobactam in tazocin injectable powder.
2002 Jul 31
Rapid high-performance liquid chromatographic assay of dorzolamide in rabbit aqueous humor.
2002 Jun
Determination of ethylenediamine tetraacetic acid in injection forms by ion-pair chromatography.
2002 Jun 15
Simultaneous determination of N-oxides and free bases of pyrrolizidine alkaloids by cation-exchange solid-phase extraction and ion-pair high-performance liquid chromatography.
2002 Mar 8
Validation of a simple liquid chromatographic method for determination and quantitation of residual ivermectin and doramectin in pig liver.
2002 Mar-Apr
[The effect of shourong compound formula on levels of dopamine and its metabolites in brain of Parkinson's disease mice induced by reserpine].
2002 May
[Determination of aspirin and free salicylic acid in lysinipirine injection by high performance liquid chromatography].
2002 May
LC-MS/MS determination of a farnesyl transferase inhibitor in human plasma and urine.
2002 Nov 7
Determination of undecylenic and sorbic acids in cosmetic preparations by high performance liquid chromatography with electrochemical detection.
2002 Nov 7
A modified HPLC method for the determination of ochratoxin A by fluorescence detection.
2002 Oct
Interaction of cytochrome P450 3A inhibitors with P-glycoprotein.
2002 Oct
Development and substantiation of a liquid chromatographic method for monitoring organic reactions involved in synthesis of 4-methoxyphenylacetic acid.
2002 Oct 4
The physiology of overwintering in a turtle that occupies multiple habitats, the common snapping turtle (Chelydra serpentina).
2002 Sep-Oct
Osteology and skeletal development of Apalone spinifera (Reptilia: Testudines: Trionychidae).
2003 Apr
Expression of heart K+ channels in adrenalectomized and catecholamine-depleted reserpine-treated rats.
2003 Feb
Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson's disease.
2003 Feb
Determination of peptides and amino acids from wool and beer with sensitive fluorescent reagent 2-(9-carbazole)-ethyl chloroformate by reverse phase high-performance liquid chromotography and liquid chromotography mass spectrometry.
2003 Feb 1
Antitumour 2-(4-aminophenyl)benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo.
2003 Feb 10
DNA damage and cell cycle arrest induced by 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) is attenuated in aryl hydrocarbon receptor deficient MCF-7 cells.
2003 Feb 24
Optimization and validation of conventional and micellar LC methods for the analysis of methyltestosterone in sugar-coated pills.
2003 Feb 5
Analysis of selected withanolides in plant extract by capillary electrochromatography and microemulsion electrokinetic chromatography.
2003 Jan
Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line.
2003 Jan 14
Analysis of flecainide and two metabolites in biological specimens by HPLC: application to a fatal intoxication.
2003 Jan-Feb
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.
2003 Jun
Rat stomach ECL cells: mode of activation of histidine decarboxylase.
2003 Jun 15
Studies on the long-term thermal stability of stationary phases in subcritical water chromatography.
2003 Mar 7
Assessment of a controlled release hydrophilic matrix formulation for metoclopramide HCl.
2003 May
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
Patents

Patents

JP2001500812A
6
JP2002539968A
6
JP2005527671A
6
JP2005533754A
6
JP2005538090A
27
JP2008538220A
6
JP2010516850A
6
JP2010527393A
6
JP2011528057A
6
JP3329816B2
6
JP3329827B2
6
JP3950631B2
6
JP4372790B2
6
JP4718179B2
6
JP4729238B2
6
JP4803937B2
6
JP4806394B2
6
JPH02300140A
17
JPS5718683A
6
JPS61257944A
6
JPS6226255A
6
JPS623794A
6

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
Substance Class Chemical
Created
by admin
on Sat Dec 16 15:07:49 GMT 2023
Edited
by admin
on Sat Dec 16 15:07:49 GMT 2023
Record UNII
OXG2LZ9MP7
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RESERPINE HYDROCHLORIDE MONOHYDRATE
Common Name English
RESERPINE HYDROCHLORIDE HYDRATE [MI]
Common Name English
YOHIMBAN-16-CARBOXYLIC ACID, 11,17-DIMETHOXY-18-((3,4,5-TRIMETHOXYBENZOYL)OXY)-, METHYL ESTER, MONOHYDROCHLORIDE, MONOHYDRATE, (3.BETA.,16.BETA.,17.ALPHA.,18.BETA.,20.ALPHA.)-
Systematic 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), MONOHYDROCHLORIDE, MONOHYDRATE
Systematic Name English
Code System Code Type Description
MERCK INDEX
m9535
Created by admin on Sat Dec 16 15:07:49 GMT 2023 , Edited by admin on Sat Dec 16 15:07:49 GMT 2023
PRIMARY
PUBCHEM
133082991
Created by admin on Sat Dec 16 15:07:49 GMT 2023 , Edited by admin on Sat Dec 16 15:07:49 GMT 2023
PRIMARY
FDA UNII
OXG2LZ9MP7
Created by admin on Sat Dec 16 15:07:49 GMT 2023 , Edited by admin on Sat Dec 16 15:07:49 GMT 2023
PRIMARY
CAS
6105-94-8
Created by admin on Sat Dec 16 15:07:49 GMT 2023 , Edited by admin on Sat Dec 16 15:07:49 GMT 2023
PRIMARY
Related Record Type Details
Structure of RESERPINE HYDROCHLORIDE
ANHYDROUS->SOLVATE
NIH
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