Page last updated: 2024-12-06

tetrahydropapaveroline

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Tetrahydropapaveroline (THP) is a naturally occurring tetrahydroisoquinoline alkaloid that has been identified in various plants and in human brain tissue. It is synthesized in vivo from dopamine and an aldehyde derived from catechol-O-methyltransferase (COMT) metabolism. THP has been implicated in the development of Parkinson's disease due to its ability to inhibit monoamine oxidase (MAO), an enzyme involved in the breakdown of dopamine. In addition, THP has been shown to act as an agonist at opioid receptors, suggesting a potential role in the development of drug addiction. The synthesis of THP is of interest in understanding its role in various physiological processes, including neurotransmission, dopamine metabolism, and the development of neurodegenerative diseases. The effects of THP are still under investigation, but it is known to be neurotoxic and potentially carcinogenic. Its importance lies in its connection to Parkinson's disease, drug addiction, and other neurological disorders. Research on THP aims to elucidate its mechanisms of action, identify its potential therapeutic uses, and develop strategies to prevent or treat its detrimental effects.'

Tetrahydropapaveroline: A leukomaine (animal alkaloid) formed in brain and liver from dopamine and L-dopa; it may be implicated in psychiatric problems. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID18519
CHEMBL ID19068
CHEBI ID28770
SCHEMBL ID221137
MeSH IDM0021235

Synonyms (33)

Synonym
1-(3,4-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol
CHEBI:28770 ,
tetrahydropapaveroline
C06350
4747-99-3
(r,s)-norlaudanosoline
norlaudanosoline
OPREA1_179526
6,7-isoquinolinediol, 1-((3,4-dihydroxyphenyl)methyl)-1,2,3,4-tetrahydro-
tetrahydroxypapaveroline
CHEMBL19068 ,
1-[(3,4-dihydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol
bdbm50027331
1-[(3,4-dihydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydrobromide (jw8-5)
unii-v1ewj6b8ky
v1ewj6b8ky ,
(+/-)-tetrahydropapaveroline
SCHEMBL221137
ABXZOXDTHTTZJW-UHFFFAOYSA-N
papaveroline, 1,2,3,4-tetrahydro-
1-(3,4-dihydroxybenzyl)-1,2,3,4-tetrahydro-6,7-isoquinolinediol #
1-((3,4-dihydroxyphenyl)methyl)-1,2,3,4-tetrahydro-6,7-isoquinolinediol
(rs)-norlaudanosoline
tetrahydropapaveroline, (+/-)-
(+/-)-norlaudanosoline
tetrahydropapaveroline [mi]
Z2752228094
6,7-dihydroxy-1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline
Q27103884
DTXSID70963850
STL565699
AKOS037623582
norlaudanosoline hydrobromide salt

Research Excerpts

Overview

Tetrahydropapaveroline (THP) is a compound derived from dopamine monoamine oxidase-mediated metabolism. It is present in the brain of parkinsonian patients receiving L-dopa therapy, and is capable of causing dopaminergic neurodegeneration.

ExcerptReferenceRelevance
"Tetrahydropapaveroline (THP), which is an endogenous neurotoxin, has been suspected to be associated with dopaminergic neurotoxicity of l-DOPA. "( Oxidative modification of neurofilament-L and neuronal cell death induced by the catechol neurotoxin, tetrahydropapaveroline.
Choi, SY; Eum, WS; Kang, JH; Kyeong, IG, 2013
)
2.05
"Tetrahydropapaveroline (THP) is a compound derived from dopamine monoamine oxidase-mediated metabolism, particularly present in the brain of parkinsonian patients receiving L-dopa therapy, and is capable of causing dopaminergic neurodegeneration. "( Study on the ability of 1,2,3,4-tetrahydropapaveroline to cause oxidative stress: Mechanisms and potential implications in relation to parkinson's disease.
Hermida-Ameijeiras, A; Méndez-Alvarez, E; Sánchez-Iglesias, S; Sánchez-Sellero, I; Sanmartín-Suárez, C; Soto-Otero, R, 2006
)
2.06
"Tetrahydropapaveroline is an endogenous complex alkaloid derived from dopamine through the oxidation by monoamine oxidase. "( Enantio-selective occurrence of (S)-tetrahydropapaveroline in human brain.
Dostert, P; Kawai, M; Maruyama, W; Matsubara, K; Minami, C; Naoi, M; Sango, K, 2000
)
2.02

Dosage Studied

ExcerptRelevanceReference
" The current report provides a replicatin of the original experiments and also an extension of the work to complete dose-response curves for salsolinol and THP."( A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats.
Deitrich, RA; Duncan, C, 1980
)
0.26
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
benzylisoquinoline alkaloidAny isoquinoline alkaloid based on a benzylisoquinoline skeleton.
benzyltetrahydroisoquinoline
isoquinolinol
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (10)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Beta-2 adrenergic receptorRattus norvegicus (Norway rat)Ki0.30000.00050.35461.6000AID41753
Alpha-1B adrenergic receptorRattus norvegicus (Norway rat)Ki40.00000.00010.949010.0000AID33138
Beta-1 adrenergic receptorRattus norvegicus (Norway rat)Ki0.30000.00000.667310.0000AID41753
Alpha-2B adrenergic receptorRattus norvegicus (Norway rat)Ki40.00000.00000.929610.0000AID33138
Alpha-2C adrenergic receptorRattus norvegicus (Norway rat)Ki40.00000.00000.970810.0000AID33138
Alpha-2A adrenergic receptorRattus norvegicus (Norway rat)Ki40.00000.00000.937510.0000AID33138
Alpha-1D adrenergic receptorRattus norvegicus (Norway rat)Ki40.00000.00000.575110.0000AID33138
Beta-3 adrenergic receptorRattus norvegicus (Norway rat)Ki0.30000.00050.33671.6000AID41753
Adenosine receptor A2aRattus norvegicus (Norway rat)Ki40.00000.00021.494010.0000AID33138
Alpha-1A adrenergic receptorRattus norvegicus (Norway rat)Ki40.00000.00000.965010.0000AID33138
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Molecular Functions (1)

Processvia Protein(s)Taxonomy
G protein-coupled adenosine receptor activityAdenosine receptor A2aRattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (1)

Processvia Protein(s)Taxonomy
Golgi membraneAdenosine receptor A2aRattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (13)

Assay IDTitleYearJournalArticle
AID41289Beta adrenergic receptor agonist activity a in guinea pig, isolated, carbachol-contracted tracheal preparations1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID41304Beta adrenergic receptor antagonistic activity in reserpine pre-treated guinea pig, isolated, spontaneously beating, right atrial preparation; NA = No antagonism of isoproterenol responses up to 2.2 x 10E-8 mol/L1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID231770Ratio of compound Emax(50) to that of isoproterenol Emax(50) in guinea pig, isolated, spontaneously beating, right atrial preparation; Expressed as drug Emax(50)/Iso Emax(50) mean1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID41293Beta adrenergic receptor agonist activity in reserpine pre-treated guinea pig, isolated, spontaneously beating, right atrial preparation1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID41301Beta adrenergic receptor antagonistic activity in guinea pig, isolated, carbachol-contracted tracheal preparations; NA = No antagonism of isoproterenol responses up to 2.2 x 10E-8 mol/L1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID41310Beta adrenergic receptor agonist activity in guinea pig, isolated, carbachol-contracted tracheal preparations1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID33138Inhibition of [3H]WB-4101 binding to alpha adrenergic receptor from rat cerebral cortical membranes1980Journal of medicinal chemistry, Jun, Volume: 23, Issue:6
Mammalian alkaloids. 8. Synthesis and biological effects of tetrahydropapaveroline related 1-benzyltetrahydroisoquinolines.
AID41753Inhibition of [3H]dihydroalprenolol binding to Beta adrenergic receptor from rat cerebral cortical membranes1980Journal of medicinal chemistry, Jun, Volume: 23, Issue:6
Mammalian alkaloids. 8. Synthesis and biological effects of tetrahydropapaveroline related 1-benzyltetrahydroisoquinolines.
AID231771Ratio of compound Emax(50) to that of isoproterenol Emax(50) in reserpine-pretreated, guinea pig, isolated, spontaneously beating, right atrial preparation; Expressed as drug Emax(50)/Iso Emax(50) mean1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID41311Beta adrenergic receptor agonist activity in guinea pig, isolated, spontaneously beating, right atrial preparation1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID63017Inhibition of [3H]spiroperidol binding to dopamine receptor from rat striatum membranes1980Journal of medicinal chemistry, Jun, Volume: 23, Issue:6
Mammalian alkaloids. 8. Synthesis and biological effects of tetrahydropapaveroline related 1-benzyltetrahydroisoquinolines.
AID41292Beta adrenergic receptor agonist activity in guinea pig, isolated, spontaneously beating, right atrial preparation1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
AID41312Beta adrenergic receptor agonist activity in reserpine pre-treated guinea pig, isolated, spontaneously beating, right atrial preparation1983Journal of medicinal chemistry, Apr, Volume: 26, Issue:4
Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (123)

TimeframeStudies, This Drug (%)All Drugs %
pre-199063 (51.22)18.7374
1990's24 (19.51)18.2507
2000's22 (17.89)29.6817
2010's12 (9.76)24.3611
2020's2 (1.63)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 20.99

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index20.99 (24.57)
Research Supply Index4.95 (2.92)
Research Growth Index4.29 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (20.99)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews3 (2.14%)6.00%
Case Studies1 (0.71%)4.05%
Observational0 (0.00%)0.25%
Other136 (97.14%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]