10-hydroxynortriptyline profile

## 10-Hydroxynortriptyline (10-OH-NT)

10-Hydroxynortriptyline (10-OH-NT) is a **metabolite of the tricyclic antidepressant nortriptyline**. It's an **active metabolite**, meaning it has its own pharmacological effects and contributes to the overall therapeutic action of nortriptyline.

**Why is it important for research?**

1. **Potential Therapeutic Benefits:**
- Research suggests that 10-OH-NT might be **more potent and have a faster onset of action** than its parent compound, nortriptyline.
- It shows **promising activity in treating major depressive disorder (MDD)** and may offer **benefits in other conditions**, like chronic pain, anxiety, and epilepsy.
- Studies are ongoing to explore its potential therapeutic applications in various conditions.

2. **Pharmacokinetic Understanding:**
- Understanding the pharmacokinetics of 10-OH-NT is crucial for **optimizing treatment regimens** and predicting individual responses to nortriptyline.
- Research on its metabolism, distribution, and elimination contributes to **developing personalized medicine approaches** for antidepressant therapy.

3. **Mechanism of Action:**
- 10-OH-NT acts as a **serotonin and norepinephrine reuptake inhibitor (SNRI)**, similar to its parent compound.
- Research aims to elucidate the specific mechanisms through which 10-OH-NT exerts its therapeutic effects, which may involve interactions with various neurotransmitter systems in the brain.

4. **Development of Novel Therapeutics:**
- The unique pharmacological profile of 10-OH-NT has sparked interest in developing **selective 10-OH-NT-based drugs**, which could potentially offer improved therapeutic efficacy and fewer side effects compared to traditional tricyclic antidepressants.

5. **Understanding Drug-Drug Interactions:**
- 10-OH-NT can interact with other medications, leading to potential side effects or altered drug efficacy.
- Research on these interactions is crucial for safe and effective polypharmacy, especially in patients taking multiple medications.

**Overall, research on 10-OH-NT is vital for furthering our understanding of antidepressant mechanisms, developing novel therapies, and optimizing the use of existing medications.** It holds potential for improving patient outcomes and addressing unmet medical needs in the treatment of various conditions.

10-hydroxynortriptyline: RN given refers to cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	6420504
CHEMBL ID	3638287
MeSH ID	M0061411

Synonym
10-hydroxynortriptyline
1156-99-6
5h-dibenzo(a,d)cyclohepten-10-ol, 10,11-dihydro-5-(3-(methylamino)propylidene)-, (z)-
(z)-10,11-dihydro-5-(3-(methylamino)propylidene)-5h-dibenzo(a,d)cyclohepten-10-ol
47132-19-4
unii-7a43otr1b8
10-hydroxynortriptyline, (z)-
cis-10-hydroxynortriptyline
10-hydroxy-(z)-nortriptyline
7a43otr1b8 ,
10,11-dihydro-5-(3-(methylamino)propylidene)-5h-dibenzo(a,d)cyclohepten-10-ol
cis-10-hydroxy nortriptyline
(z)-10-hydroxynortriptyline
AKOS015903323
VAGXZGJKNUNLHK-WJDWOHSUSA-N
CHEMBL3638287
(5z)-10,11-dihydro-5-(3-(methylamino)propylidene)-5h-dibenzo(a,d)cyclohepten-10-ol
5h-dibenzo(a,d)cyclohepten-10-ol, 10,11-dihydro-5-(3-(methylamino)propylidene)-, (5z)-
cis-10-hydroxy nortriptyline-d3
(-)-z-10-oh-nt
dqq770f8uo ,
10-hydroxynortriptyline, (z)-(-)-
unii-dqq770f8uo
(+)-z-10-oh-nt
unii-411i184mg3
10-hydroxynortriptyline, (z)-(+)-
115460-06-5
5h-dibenzo(a,d)cyclohepten-10-ol, 10,11-dihydro-5-(3-(methylamino)propylidene)-, (5z)-(-)-
411i184mg3 ,
5h-dibenzo(a,d)cyclohepten-10-ol, 10,11-dihydro-5-(3-(methylamino)propylidene)-, (5z)-(+)-
115460-05-4
nortriptyline metabolite(+/-)-(z)
(2z)-2-[3-(methylamino)propylidene]tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-9-ol
(z)-5-(3-(methylamino)propylidene)-10,11-dihydro-5h-dibenzo[a,d][7]annulen-10-ol
XBA13219

Excerpt	Reference	Relevance
" Coupled with its low affinity for muscarinic receptors, these kinetic and pharmacodynamic features of E-10-OH-NT call for further phase I studies."	( Disposition of single oral doses of E-10-hydroxynortriptyline in healthy subjects, with some observations on pharmacodynamic effects. Bertilsson, L; Nordin, C; Otani, K; Resul, B; Scheinin, M; Siwers, B; Sjöqvist, F, 1986)	0.54
" Evaluation of free, instead of total levels did not help to clarify the relationship between clinical and pharmacokinetic variables."	( Antidepressive effect and pharmacokinetics of amitriptyline with consideration of unbound drug and 10-hydroxynortriptyline plasma levels. Breyer-Pfaff, U; Brinkschulte, M; Gaertner, HJ; Kreuter, F; Scharek, G; Wiatr, R, 1982)	0.48
"Subjects who were homozygous for CYP2D610 had significantly higher total areas under the plasma concentration-time curve (AUC), lower apparent oral clearances, and longer mean plasma half-life of nortriptyline than subjects in the CYP2D61/*1 and the heterozygous groups."	( Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes. Bertilsson, L; Dahl, ML; Dalén, P; Sjöqvist, F; Tybring, G; Yue, QY; Zhong, ZH, 1998)	0.3
" At the end of each study week, the steady-state pharmacokinetic parameters of nortriptyline or paroxetine were determined within the dose interval."	( Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Andersson, K; Bertilsson, L; Härtter, S; Laine, K; Svensson, JO; Tybring, G; Widén, J, 2001)	0.31
" The developed assay was applied to a pharmacokinetic study in humans."	( Development and validation of a highly sensitive LC-MS/MS method for simultaneous quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma: application to a human pharmacokinetic study. Bharathi, DV; Hotha, KK; Jagadeesh, B; Kumar, KK; Mullangi, R; Rao, DV; Ravindranath, LK; Reddy, YR; Veera, KN, 2010)	0.57

Excerpt	Reference	Relevance
" It was assumed that pretreatment with cimetidine, because of its inhibition of metabolic pathways of both demethylation and hydroxylation as well as its ability to reduce hepatic extraction of these drugs, would increase bioavailability and decrease clearance of both drugs."	( Cimetidine interaction with imipramine and nortriptyline. Henauer, SA; Hollister, LE, 1984)	0.27
" After an acute intraperitoneal (IP) administration of amitriptyline (AMI) to male Sprague-Dawley rats we found that: (i) its absorption rate is rapid; (ii) its elimination half-life is much shorter than in humans; and (iii) its levels largely exceeded those of its metabolites."	( Plasma and brain pharmacokinetics of amitriptyline and its demethylated and hydroxylated metabolites after one and six half-life repeated administrations to rats. Besson, A; Coudore, F; Eschalier, A; Fialip, J; Lavarenne, J, 1996)	0.29

Excerpt	Relevance	Reference
"The postulated therapeutic activity of nortriptyline metabolites has prompted investigation of dosage adjustments based on plasma levels of nortriptyline (NT) and its metabolites."	( Relationships among nortriptyline, 10-OH(E)nortriptyline, and 10-OH(Z)nortriptyline steady-state plasma levels and nortriptyline dosage. Hurst, HE; Jones, DR; Lukey, BJ; Wright, JH, 1989)	0.28
" In addition, after 6 weeks of dosing patients estimated their percentage of pain in comparison with baseline."	( Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain. de Wolff, FA; Edelbroek, PM; Linssen, AC; Rooymans, HG; Zitman, FG, 1986)	0.27
" The clinical uses of TCA plasma level-response studies are discussed in relationship to rational dosage adjustment to increase response rates and avoid iatrogenic toxicity."	( Nortriptyline pharmacokinetics and plasma levels: implications for clinical practice. Biggs, JT; Preskorn, SH; Rubin, EH, 1985)	0.27
" Genotyping of subjects with multiple copies of functional genes may be of great value for differentiating ultrarapid metabolizers from patients who do not comply with the prescription and for assuring adequate drug choice and dosage for these patients."	( 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Bernal Ruiz, ML; Bertilsson, L; Dahl, ML; Dalén, P; Nordin, J, 1998)	0.3
"Paroxetine, with a daily dosage from 20 to 40 mg, is an effective tool in normalizing the metabolic status of CYP2D6 ultrarapid metabolizers."	( Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Andersson, K; Bertilsson, L; Härtter, S; Laine, K; Svensson, JO; Tybring, G; Widén, J, 2001)	0.31

Pathway	Proteins	Compounds
Amitriptyline and Nortriptyline Pathway, Pharmacokinetics	13	6

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	37 (46.84)	18.7374
1990's	30 (37.97)	18.2507
2000's	7 (8.86)	29.6817
2010's	4 (5.06)	24.3611
2020's	1 (1.27)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	13 (16.05%)	5.53%
Reviews	4 (4.94%)	6.00%
Case Studies	3 (3.70%)	4.05%
Observational	0 (0.00%)	0.25%
Other	61 (75.31%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
homovanillic acid Homovanillic Acid: A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.. homovanillate : A hydroxy monocarboxylic acid anion which is obtained by deprotonation of the carboxy group of homovanillic acid.. homovanillic acid : A monocarboxylic acid that is the 3-O-methyl ether of (3,4-dihydroxyphenyl)acetic acid. It is a catecholamine metabolite.	1.97	1	0	guaiacols; monocarboxylic acid	human metabolite; mouse metabolite
hydroxyindoleacetic acid (5-hydroxyindol-3-yl)acetic acid : A member of the class of indole-3-acetic acids that is indole-3-acetic acid substituted by a hydroxy group at C-5.	2.37	2	0	indole-3-acetic acids	drug metabolite; human metabolite; mouse metabolite
amitriptyline Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.. amitriptyline : An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(dimethylamino)propylidene group at position 5.	11.63	20	3	carbotricyclic compound; tertiary amine	adrenergic uptake inhibitor; antidepressant; environmental contaminant; tropomyosin-related kinase B receptor agonist; xenobiotic
carbamazepine Carbamazepine: A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties.. carbamazepine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant.	3.44	1	1	dibenzoazepine; ureas	analgesic; anticonvulsant; antimanic drug; drug allergen; EC 3.5.1.98 (histone deacetylase) inhibitor; environmental contaminant; glutamate transporter activator; mitogen; non-narcotic analgesic; sodium channel blocker; xenobiotic
chlordiazepoxide Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal.. chlordiazepoxide : A benzodiazepine that is 3H-1,4-benzodiazepine 4-oxide substituted by a chloro group at position 7, a phenyl group at position 5 and a methylamino group at position 2.	1.96	1	0	benzodiazepine
cimetidine Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.. cimetidine : A member of the class of guanidines that consists of guanidine carrying a methyl substituent at position 1, a cyano group at position 2 and a 2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl group at position 3. It is a H2-receptor antagonist that inhibits the production of acid in stomach.	1.96	1	0	aliphatic sulfide; guanidines; imidazoles; nitrile	adjuvant; analgesic; anti-ulcer drug; H2-receptor antagonist; P450 inhibitor
citalopram Citalopram: A furancarbonitrile that is one of the serotonin uptake inhibitors used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from TARDIVE DYSKINESIA in preference to tricyclic antidepressants, which aggravate dyskinesia.. citalopram : A racemate comprising equimolar amounts of (R)-citalopram and its enantiomer, escitalopram. It is used as an antidepressant, although only escitalopram is active.. 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile : A nitrile that is 1,3-dihydro-2-benzofuran-5-carbonitrile in which one of the hydrogens at position 1 is replaced by a p-fluorophenyl group, while the other is replaced by a 3-(dimethylamino)propyl group.	3.48	1	1	2-benzofurans; cyclic ether; nitrile; organofluorine compound; tertiary amino compound
clomipramine Clomipramine: A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.. clomipramine : A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine which is substituted by chlorine at position 3 and in which the hydrogen attached to the nitrogen is replaced by a 3-(dimethylamino)propyl group. One of the more sedating tricyclic antidepressants, it is used as the hydrochloride salt for the treatment of depression as well as obsessive-compulsive disorder and phobias.	2.03	1	0	dibenzoazepine	anticoronaviral agent; antidepressant; EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor; serotonergic antagonist; serotonergic drug; serotonin uptake inhibitor
debrisoquin Debrisoquin: An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.	5.94	5	2	carboxamidine; isoquinolines	adrenergic agent; antihypertensive agent; human metabolite; sympatholytic agent
desipramine Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.. desipramine : A dibenzoazepine consisting of 10,11-dihydro-5H-dibenzo[b,f]azepine substituted on nitrogen with a 3-(methylamino)propyl group.	1.96	1	0	dibenzoazepine; secondary amino compound	adrenergic uptake inhibitor; alpha-adrenergic antagonist; antidepressant; cholinergic antagonist; drug allergen; EC 3.1.4.12 (sphingomyelin phosphodiesterase) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; H1-receptor antagonist; serotonin uptake inhibitor
nordazepam Nordazepam: An intermediate in the metabolism of DIAZEPAM to OXAZEPAM. It may have actions similar to those of diazepam.. nordazepam : A 1,4-benzodiazepinone having phenyl and chloro substituents at positions 5 and 7 respectively; it has anticonvulsant, anxiolytic, muscle relaxant and sedative properties but is used primarily in the treatment of anxiety.	1.96	1	0	1,4-benzodiazepinone; organochlorine compound	anticonvulsant; anxiolytic drug; GABA modulator; human metabolite; sedative
doxepin Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.. doxepin : A dibenzooxepine that is 6,11-dihydrodibenzo[b,e]oxepine substituted by a 3-(dimethylamino)propylidene group at position 11. It is used as an antidepressant drug.	3.12	1	0	dibenzooxepine; tertiary amino compound	antidepressant
erythrosine Fluoresceins: A family of spiro(isobenzofuran-1(3H),9'-(9H)xanthen)-3-one derivatives. These are used as dyes, as indicators for various metals, and as fluorescent labels in immunoassays.	1.97	1	0
phenelzine Phenelzine: One of the MONOAMINE OXIDASE INHIBITORS used to treat DEPRESSION; PHOBIC DISORDERS; and PANIC.	3.36	1	1	primary amine
imipramine Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.. imipramine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)propyl group at the nitrogen atom.	1.96	1	0	dibenzoazepine	adrenergic uptake inhibitor; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor
mephenytoin Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.. mephenytoin : An imidazolidine-2,4-dione (hydantoin) in which the imidazolidine nucleus carries a methyl group at N-3 and has ethyl and phenyl substituents at C-5. An anticonvulsant, it is no longer available in the USA or the UK but is still studied largely because of its interesting hydroxylation polymorphism.	2.38	2	0	imidazolidine-2,4-dione	anticonvulsant
nortriptyline Nortriptyline: A metabolite of AMITRIPTYLINE that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions.. nortriptyline : An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(methylamino)propylidene group at position 5. It is an active metabolite of amitriptyline.	12.47	79	13	organic tricyclic compound; secondary amine	adrenergic uptake inhibitor; analgesic; antidepressant; antineoplastic agent; apoptosis inducer; drug metabolite
propranolol Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.	6.97	1	0	naphthalenes; propanolamine; secondary amine	anti-arrhythmia drug; antihypertensive agent; anxiolytic drug; beta-adrenergic antagonist; environmental contaminant; human blood serum metabolite; vasodilator agent; xenobiotic
risperidone Risperidone: A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.. risperidone : A member of the class of pyridopyrimidines that is 2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one carrying an additional 2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl group at position 2.	2.02	1	0	1,2-benzoxazoles; heteroarylpiperidine; organofluorine compound; pyridopyrimidine	alpha-adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; H1-receptor antagonist; psychotropic drug; second generation antipsychotic; serotonergic antagonist
hydantoins Hydantoins: Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS.. imidazolidine-2,4-dione : An imidazolidinone with oxo groups at position 2 and 4.	1.96	1	0	imidazolidine-2,4-dione
methoxyhydroxyphenylglycol Methoxyhydroxyphenylglycol: Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover.	2.66	3	0	methoxybenzenes; phenols
demoxepam demoxepam: structure	1.96	1	0
fluorescein Fluorescein: A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor.. fluorescein (lactone form) : A xanthene dye that is highly fluorescent, detectable even when present in minute quantities. Used forensically to detect traces of blood, in analytical chemistry as an indicator in silver nitrate titrations and in microscopy.	1.97	1	0	2-benzofurans; gamma-lactone; organic heteropentacyclic compound; oxaspiro compound; polyphenol; xanthene dye	fluorescent dye; radioopaque medium
n-demethylchlordiazepoxide [no description available]	1.96	1	0
deuterium Deuterium: The stable isotope of hydrogen. It has one neutron and one proton in the nucleus.	1.99	1	0	dihydrogen
paroxetine Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression.. paroxetine : A benzodioxole that consists of piperidine bearing 1,3-benzodioxol-5-yloxy)methyl and 4-fluorophenyl substituents at positions 3 and 4 respectively; the (3S,4R)-diastereomer. Highly potent and selective 5-HT uptake inhibitor that binds with high affinity to the serotonin transporter (Ki = 0.05 nM). Ki values are 1.1, 350 and 1100 nM for inhibition of [3H]-5-HT, [3H]-l-NA and [3H]-DA uptake respectively. Displays minimal affinity for alpha1-, alpha2- or beta-adrenoceptors, 5-HT2A, 5-HT1A, D2 or H1 receptors at concentrations below 1000 nM, however displays weak affinity for muscarinic ACh receptors (Ki = 42 nM). Antidepressant and anxiolytic in vivo.	4.16	3	1	aromatic ether; benzodioxoles; organofluorine compound; piperidines	antidepressant; anxiolytic drug; hepatotoxic agent; P450 inhibitor; serotonin uptake inhibitor
4-hydroxydebrisoquin 4-hydroxydebrisoquin: principal metabolite of above; RN given refers to parent cpd. 4-hydroxydebrisoquin : An isoquinoline that is 3,4-dihydroisoquinoline bearing amidino and hydroxy substituent at positions 2 and 4 respectively.	3.39	1	1	carboxamidine; isoquinolines; secondary alcohol	metabolite
quinidine Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.. quinidine : A cinchona alkaloid consisting of cinchonine with the hydrogen at the 6-position of the quinoline ring substituted by methoxy.	6.97	1	0	cinchona alkaloid	alpha-adrenergic antagonist; anti-arrhythmia drug; antimalarial; drug allergen; EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor; EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor; muscarinic antagonist; P450 inhibitor; potassium channel blocker; sodium channel blocker
cocaine Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.. cocaine : A tropane alkaloid obtained from leaves of the South American shrub Erythroxylon coca.	1.97	1	0	benzoate ester; methyl ester; tertiary amino compound; tropane alkaloid	adrenergic uptake inhibitor; central nervous system stimulant; dopamine uptake inhibitor; environmental contaminant; local anaesthetic; mouse metabolite; plant metabolite; serotonin uptake inhibitor; sodium channel blocker; sympathomimetic agent; vasoconstrictor agent; xenobiotic
riboflavin vitamin B2 : Any member of a group of vitamers that belong to the chemical structural class called flavins that exhibit biological activity against vitamin B2 deficiency. Symptoms associated with vitamin B2 deficiency include glossitis, seborrhea, angular stomaitis, cheilosis and photophobia. The vitamers include riboflavin and its phosphate derivatives (and includes their salt, ionised and hydrate forms).	1.96	1	0	flavin; vitamin B2	anti-inflammatory agent; antioxidant; cofactor; Escherichia coli metabolite; food colouring; fundamental metabolite; human urinary metabolite; mouse metabolite; photosensitizing agent; plant metabolite
desmethylclomipramine desmethylclomipramine: RN given refers to parent cpd	2.03	1	0	dibenzoazepine
nadp [no description available]	2.38	2	0
quinine [no description available]	1.97	1	0	cinchona alkaloid	antimalarial; muscle relaxant; non-narcotic analgesic
desmethyldoxepin desmethyldoxepin: active metabolite if doxepin; RN given refers to cpd without isomeric designation. desmethyldoxepin : A dibenzooxepine resulting from the demethylation of the antidepressant doxepin. It is the active metabolite of doxepin.. (Z)-desmethyldoxepin : The (Z)-isomer of desmethyldoxepin.	3.12	1	0	desmethyldoxepin
dextromethorphan Dextromethorphan: Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.. dextromethorphan : A 6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene in which the sterocenters at positions 4a, 10 and 10a have S-configuration. It is a prodrug of dextrorphan and used as an antitussive drug for suppressing cough.	1.98	1	0	6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene	antitussive; environmental contaminant; neurotoxin; NMDA receptor antagonist; oneirogen; prodrug; xenobiotic
10-hydroxyamitriptyline 10-hydroxyamitriptyline: metabolite of amitryptyline; RN given refers to parent cpd without isomeric designation	4.86	8	1	organic tricyclic compound
cyclosporine Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).	2.02	1	0

Condition	Relationship Strength	Studies	Trials
Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders.	2.68	3	0
Alcohol Abuse [description not available]	2.05	1	0
Suffocation [description not available]	2.05	1	0
Bruise [description not available]	2.05	1	0
Petechiae Pinhead size (3 mm) skin discolorization due to hemorrhage.	2.05	1	0
Facial Injuries General or unspecified injuries to the soft tissue or bony portions of the face.	2.05	1	0
Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)	2.05	1	0
Asphyxia A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life.	2.05	1	0
Contusions Injuries resulting in hemorrhage, usually manifested in the skin.	2.05	1	0
Purpura Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. When the size of the discolorization is	2.05	1	0
Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)	3.81	2	1
Birth Weight The mass or quantity of heaviness of an individual at BIRTH. It is expressed by units of pounds or kilograms.	2.03	1	0
Depression, Involutional Form of depression in those MIDDLE AGE with feelings of ANXIETY.	2.42	2	0
Complications, Pregnancy [description not available]	2.41	2	0
Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5)	2.42	2	0
Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	2.41	2	0
Depression, Endogenous [description not available]	8.8	28	5
Depressive Disorder An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.	8.8	28	5
Cardiac Failure [description not available]	1.96	1	0
Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.	6.96	1	0
Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	2.66	3	0
Chronic Kidney Failure [description not available]	1.96	1	0
Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.	1.96	1	0
Behavior Disorders [description not available]	1.98	1	0
Mental Disorders Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.	1.98	1	0
Affective Psychosis, Bipolar [description not available]	2.4	2	0
Bipolar Disorder A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.	2.4	2	0
Post-Natal Depression [description not available]	1.99	1	0
Depression, Postpartum Depression in POSTPARTUM WOMEN, usually within four weeks after giving birth (PARTURITION). The degree of depression ranges from mild transient depression to neurotic or psychotic depressive disorders. (From DSM-IV, p386)	1.99	1	0
Alloxan Diabetes [description not available]	1.99	1	0
Adjustment Disorder [description not available]	2	1	0
Adjustment Disorders Maladaptive reactions to identifiable psychosocial stressors occurring within a short time after onset of the stressor. They are manifested by either impairment in social or occupational functioning or by symptoms (depression, anxiety, etc.) that are in excess of a normal and expected reaction to the stressor.	2	1	0
Hypotension, Postural [description not available]	3.39	1	1
Action Tremor [description not available]	3.39	1	1
Asialia [description not available]	3.39	1	1
Hypotension, Orthostatic A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.	3.39	1	1
Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.	3.39	1	1
Xerostomia Decreased salivary flow.	3.39	1	1
Arrhythmia [description not available]	4.05	3	1
Cardiac Output, Low A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.	1.98	1	0
Cardiac Diseases [description not available]	1.98	1	0
Arrhythmias, Cardiac Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.	4.05	3	1
Heart Diseases Pathological conditions involving the HEART including its structural and functional abnormalities.	1.98	1	0
Puerperal Disorders Disorders or diseases associated with PUERPERIUM, the six-to-eight-week period immediately after PARTURITION in humans.	1.97	1	0
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	1.97	1	0
Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (IRIS DISEASES) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease.	1.97	1	0
Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	1.97	1	0
Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).	1.97	1	0
Chronic Illness [description not available]	3.35	1	1
Ache [description not available]	3.35	1	1
Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).	3.35	1	1
Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.	3.35	1	1

10-hydroxynortriptyline

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Research Demand Index: 17.39

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