How Can I Use Duloxetine for Depression?

Duloxetine is a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor. The results of preclinical studies show that duloxetine is a strong inhibitor of neuronal 5-HT and NE reuptake, and its inhibitory effect on dopamine reuptake is relatively weak. In vitro studies have shown that duloxetine has no significant affinity with dopaminergic receptors, adrenergic receptors, cholinergic receptors, histaminergic receptors, opioid receptors, glutamate receptors, and GABA receptors. Duloxetine does not inhibit monoamine oxidase.

Chinese name: B

Foreign name: Duloxetine
Drug classification: Antipsychotic, antidepressant, anxiolytic drugs

Duloxetine Basic Information

Chinese name

Chinese alias: (R)-(-)-N-methyl-3- (1-naphthyloxy) -3- (2-thiophene) -propylamine; Dextraloxetine hydrochloride

English name: (3R) -N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine

English alias: Ariclaim; N-methyl-3-napthalen-1-oxy-3-thiophen-2-yl-1-amine; R-Duloxetine HCl; UNII-TK9VOT90JQ; Cymbalta

CAS number: 116539-60-7

Molecular formula: C ₁₈ H ₂₀ ClNOS

Molecular weight: 333.87600

Exact mass: 333.09500

PSA: 49.50000

LogP: 5.82380

Structural formula:

Physicochemical properties of Duloxetine

Density: 1.158g / cm ³

Boiling point: 466.2ºC at 760 mmHg

Flash point: 235.7ºC ^[2]

Duloxetine molecular structure data

1. Molar refractive index: 91.14

2. Molar volume (cm ³ / mol): 256.8

3. Isometric Zhang Rong (90.2K): 669.0

4. Surface tension (dyne / cm): 46.0

5. Polarizability (10-24cm ³ ): 36.13

Duloxetine calculated chemical data

1. Hydrophobic parameter calculation reference value (XlogP): 4.3

2. Number of hydrogen-bonded donors: 1

3. Number of hydrogen bond acceptors: 3

4. Number of rotatable chemical bonds: 6

5. Number of tautomers: none

6. Topological molecular polar surface area 49.5

7. Number of heavy atoms: 21

8. Surface charge: 0

9. Complexity: 312

10. Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 1

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1

Duloxetine Properties and Stability

Duloxetine Hydrochloride: C ₁₈ H ₁₉ NOS · HCI. [136434-34-9]. White solid. The pKa of dimethylformamide-water (66:34) is 9.6 ^[1] .

Duloxetine synthesis method

The following thiophene compounds were subjected to Marmieh reaction, and then subjected to asymmetric reduction with Yarnaguchi-Masher-Pohland (YMP) complex reagent LiAl ₂ H ₂ in ether at -78 ° C, and then hydrobromic acid was added to reduce the reduction product to hydrobromide Get it. It is then alkylated with 1-fluoronaphthalene and finally demethylated. The product is obtained as oxalate.

Duloxetine Duloxetine Related Drug Sheet Information

Duloxetine drug dosage form

1. Duloxetine capsules: 20mg, 30mg, 40mg, 60mg. Storage method: Store at room temperature. 2. Duloxetine enteric-coated tablets. 3. Duloxetine enteric-coated capsules.

Duloxetine pharmacological effects

Duloxetine is a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor. The mechanism of duloxetine's antidepressant and central analgesic effects has not been clarified, but it is believed that it is related to its enhancement of the serotoninergic and noradrenergic functions of the central nervous system. The results of preclinical studies show that duloxetine is a strong inhibitor of neuronal 5-HT and NE reuptake, and has relatively weak inhibitory effect on dopamine reuptake. In vitro studies have shown that duloxetine has no significant affinity with dopaminergic receptors, adrenergic receptors, cholinergic receptors, histaminergic receptors, opioid receptors, glutamate receptors, and GABA receptors. Duloxetine does not inhibit monoamine oxidase.

Duloxetine Pharmacokinetics

This medicine takes effect within 3 weeks of oral treatment of depression, the peak time is 4-6 hours, and the effect of multiple dose administration can last more than 7 days. The peak time of plasma concentration is 6 ~ 10h. The oral bioavailability of this medicine is higher than 70%, the total protein binding rate is higher than 95%, and the apparent distribution volume is 1640L. In liver metabolism, the metabolites are desmethyl duloxetine and hydroxylated metabolites. The renal excretion rate of this drug is 77%, which is mainly excreted in the form of metabolites; 15% is excreted with feces. The overall clearance rate is 114L / h, and the elimination half-life of the original drug is 11-16 hours.

Duloxetine indication

1. For the treatment of major depression. 2. For diabetic peripheral neuralgia. 3. For women with moderate to severe stress incontinence.

Duloxetine contraindications

1. Those who are allergic to this medicine. 2. Patients with uncontrolled narrow-angle glaucoma. 3. Not recommended for liver dysfunction.

Duloxetine precautions

1. Use with caution: (1) Patients with controlled narrow-angle glaucoma. (2) Patients with epilepsy. (3) Patients with active mania or hypomania. (4) Suicidal depression patients. (5) Those with renal insufficiency. 2. The effect of the drug on pregnancy: the use of this drug during pregnancy can cause serious complications in the newborn (respiratory distress, asphyxia, cyanosis, seizures, unstable body temperature, vomiting, hypoglycemia, decreased or increased muscle tone, reflection Hyperthyroidism, neurotic tremor, and irritability). The U.S. Drug and Food Administration (FDA) rates the drug's pregnancy safety level C. 3. The effects of drugs on breastfeeding: it is not clear. 4. This drug is forbidden to be combined with serotoninergic drugs. 5. If the blood pressure continues to rise, it should be closely monitored. 6. Withdrawal should be gradually reduced. Sudden withdrawal may lead to withdrawal syndrome.

Duloxetine adverse reactions

1. Cardiovascular system: It can cause a slight increase in blood pressure and a decrease in heart rate, and even a continuous rise in blood pressure. 2. Central nervous system: Insomnia, headache, drowsiness, dizziness, tremor and irritability are visible. 3. Metabolic / endocrine system: visible weight loss. 4. Urogenital system: Difficult urination and male sexual dysfunction (such as ejaculation disorder, decreased libido, erectile dysfunction, delayed ejaculation, orgasmic dysfunction) can be seen. 5. Gastrointestinal tract: Nausea, diarrhea, constipation, dry mouth, poor appetite, and taste changes can be seen. 6. Blood: Anemia, leukopenia, increased white blood cell count, lymphadenopathy, and thrombocytopenia are rare. 7. Skin: night sweats, itching, and rash are common. Less common are acne, hair loss, cold sweat, ecchymosis, eczema, erythema, facial edema, and photosensitivity. An increase in sweating was also seen (6%). 8. Eye: Visible vision (4%).

Duloxetine dosage

Adults: 1. Oral administration at regular doses: (1) Depression: 20-30 mg once, twice daily. 60mg a day, take the meal. (2) Diabetic neuralgia: 60 mg per day, taken on a daily basis. For patients who may develop tolerance, the starting dose may be reduced. (3) Moderate to severe stress urinary incontinence in women: the initial dose is 40 mg once, twice daily, and if it is intolerable, the dose is reduced to 20 mg once daily, twice daily. 2. Dose for renal insufficiency. For renal insufficiency, a lower starting dose should be used, gradually increasing. Not recommended for patients with end-stage renal disease (requires dialysis) or severe renal impairment (creatinine clearance less than 30ml / min).

Corresponding effects of duloxetine drugs

1. Both this drug and monoamine oxidase inhibitors (MAOIs) inhibit 5-HT metabolism. The combination of the two drugs is prone to serious adverse reactions, such as central neurotoxicity or 5-HT syndrome (its clinical manifestations are hypertension, high fever, myoclonus , Irritability and irritability, hyperreflexia, sweating, chills, and tremors), and even death. It is forbidden to use this medicine in combination with MAOIs; this medicine can only be used after 14 days of disabling; 2. Capreomycin, enoxacin, fluvoxamine, and quinidine can inhibit the metabolism of the drug, increase the blood concentration (or bioavailability) and toxicity of the drug. The combination of the two needs to monitor adverse reactions. Reduce the dose of this medicine. 3. This medicine is used in combination with fluoxetine and paroxetine to inhibit metabolism. The bioavailability and blood concentration of the two medicines are increased, and the risk of serious adverse reactions is increased. The dose of the two medicines should be adjusted when combined. 4. This drug can inhibit the metabolism of tricyclic antidepressants (such as amitriptyline). The combination of the two drugs can increase the bioavailability, blood concentration and toxicity of the latter. If concomitant use is necessary, blood levels of tricyclic antidepressants, symptoms and signs of poisoning (anticholinergic effects, excessive sedation, confusion, and arrhythmia) should be closely monitored. 5. This medicine can inhibit the metabolism of phenothiazines (perphenazine) and increase the blood concentration and toxicity of the latter (excessive sedation, disturbance of consciousness, arrhythmia, orthostatic hypotension, high fever and extrapyramidal reactions) . The combination of both should be monitored for adverse reactions and the dose should be reduced if necessary. 6. This drug can inhibit the metabolism of thioridazine, increase the latter's blood concentration and cardiotoxicity (prolonged QT interval, apical torsional ventricular tachycardia, cardiac arrest), and the two should not be used in combination. 7. This medicine can inhibit the metabolism of class Ic antiarrhythmic drugs and increase the latter's blood concentration and cardiotoxicity. The combination of the two should closely monitor the blood concentration and electrocardiogram of class Ic antiarrhythmic drugs. 8. The combination of the drug and the central nervous system inhibitory drug can cause the deterioration of psychomotor disorders, and the combination of the two is prohibited. Food does not affect the peak plasma concentration of this drug, but it can slow absorption and reduce absorption by 10% ^[3] .