What Is Sulpiride?

Sulpiride is a white or off-white crystalline powder; odorless and slightly bitter. Slightly soluble in ethanol or propanol, very slightly soluble in chloroform, almost insoluble in water; easily soluble in sodium hydroxide solution. Melting point 177 ~ 180 ° C.

Sulpiride is a white or off-white crystalline powder; odorless and slightly bitter. Slightly soluble in ethanol or propanol, very slightly soluble in chloroform, almost insoluble in water; easily soluble in sodium hydroxide solution. Melting point 177 ~ 180 ° C.

Chinese name

Shubili

Foreign name

sulpiride

CAS number

15676-16-1

Molecular formula

C15H23N3O4S

Brief introduction of Shubili compound

Sulpi Basic Information

Chinese name

Chinese alias: (±)-Zhinailing;

English name: sulpiride

English alias: Sulpiride; (±) -Sulpiride;

CAS number: 15676-16-1

MDL number: MFCD00055061

EINECS number: 239-753-7

RTECS number: BZ3400000

PubChem number: 24277933

Molecular formula: C ₁₅ H ₂₃ N ₃ O ₄ S

Structural formula:

Molecular weight: 341.442600

Exact mass: 341.14100

PSA: 110.11000

LogP: 2.66660

Physical properties

Appearance and properties: white crystalline powder

Density: 1.236g / cm ³

Melting point: 180-185ºC

Stability: Stable at normal temperatures and pressures.

Storage conditions: 2-8ºC

Safely Safety Information

Customs Code: 29350009090

Danger category code: R36 / 37/38

Safety instructions: S26; S36 ^[1]

Sulpirid toxicology data

The median lethal dose (mouse, oral) is 2250 mg / kg.

Sulpi Calculates Chemical Data

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 2

3.Number of hydrogen bond acceptors: 6

4.Number of rotatable chemical bonds: 6

5.Number of tautomers: 2

6. Topological molecular polar surface area 110

7.Number of heavy atoms: 23

8.Surface charge: 0

9.Complexity: 505

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 0

12. Uncertain number of atomic stereocenters: 1

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1 ^[2]

Shubili uses

Biochemical research. Medicine (antipsychotic and antiemetic) ^[2]

Pharmacopoeia Standard

Source of Sulpiride (name), content (potency)

This product is N-[(1-ethyl-2-pyrrolidinyl) methyl] -2-methoxy-5- (aminosulfonyl) benzamide. Calculated on dry basis, containing C15H23N3O4S shall not be less than 98.0%.

Shubili Traits

This product is white or off-white crystalline powder; odorless and slightly bitter.

This product is slightly soluble in ethanol or acetone, very slightly soluble in chloroform, almost insoluble in water; easily soluble in sodium hydroxide solution.

Sulpiride

The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 177-180 ° C.

Shubili identification

(1) Take about 0.5g of this product, add 3ml of sodium hydroxide solution (3 10), heat, and the generated gas can make the wet red litmus test paper turn blue.

(2) Take about 0.1g of this product, add 0.1mol / L sulfuric acid solution to dissolve and dilute to 100ml, take 5ml, dilute with water to 50ml, shake well, and apply UV-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 edition) It was determined that there was a maximum absorption at a wavelength of 291 nm.

(3) The infrared absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Medicine" 510).

Shubili check

Alkalinity

Take the saturated aqueous solution of this product and check it according to law (Appendix VI H of the second edition of the Pharmacopoeia 2010), the pH value should be 8.0 ~ 10.0.

relative substance

Take an appropriate amount of this product, add the mobile phase to dissolve and dilute it to make a solution containing about 1mg per 1ml as the test solution; take 1ml precisely, place it in a 100ml volumetric flask, dilute to the mark with the mobile phase, and shake as Control solution. According to the high performance liquid chromatography (2010 Pharmacopoeia Part II Appendix VD) test, use octadecylsilane bonded silica as a filler, and potassium dihydrogen phosphate buffer solution (take 6.8 g of potassium dihydrogen phosphate, octane sulfonic acid Sodium 1g, add 1000ml of water to dissolve, adjust the pH value to 3.3 with phosphoric acid-acetonitrile-methanol (80:10:10) as the mobile phase, the detection wavelength is 240nm, the theoretical number of plates according to the Shubili peak calculation is not less than 1000. Take 10 l of the control solution and inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the sulpiride chromatographic peak is about 30% of the full scale. Then accurately measure 10 l each of the test solution and the control solution, and inject them into the liquid chromatograph respectively, and record the chromatogram to 2.5 times the peak retention time of the main component. If there are impurity peaks in the chromatogram of the test solution, the sum of the area of each impurity peak must not be greater than 0.3 times (0.3%) the area of the main peak of the control solution.

Loss on drying

Take this product and dry it at 105 to constant weight, and the weight loss shall not exceed 0.5% (Appendix L of Part Two of the Pharmacopoeia of 2010 Edition).

Residue on ignition

Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.

Heavy metal

Take the residue left under the burning residue and inspect it according to law (Appendix H of the 2010 edition of the Pharmacopoeia, the second method). The heavy metal must not exceed 10 parts per million.

Determination of sulpiride

Take about 0.25g of this product, accurately weigh, add 20ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with perchloric acid titrant (0.1mol / L) until the solution becomes blue, and titrate the The results were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 34.14mg of C15H23N3O4S. ^[3]

Shubili Pharmacology

Sulbisudil is a sulfonamide derivative. It is a selective antagonist of central dopamine (D2, D3, D4) receptors. It has strong antipsychotic and antiemetic effects, as well as mental stimulation. It has a good effect on the symptoms of indifference, flinching, stiffness, depression, hallucinations, delusions, but no obvious sedative effect and anti-manic effect. ^[4]

Sulpiride pharmacokinetics

After oral administration of sulpiride, it was slowly absorbed from the gastrointestinal tract and quickly distributed in various tissues. Peak blood drug was reached in 1 to 3 hours, and t1 / 2 was 8 to 9 hours. Mainly excreted with urine is the original drug. Its protein binding rate is less than 40%, and it can enter milk, and few enter CSF. ^[4]

Sulpiride indications

1. Depression, symptomatic psychosis, functional depression and suspected state of schizophrenia, alcoholism psychosis, mental retardation with personality disorder, senile psychosis, especially with indifference, withdrawal, stiffness, Patients with symptoms such as depression, hallucinations, doubts and delusions.

2. For antiemetic, benign peptic ulcer and ulcerative colitis. As a central antiemetic, it has a strong antiemetic effect. Oral is 166 times stronger than chlorpromazine, 142 times stronger when injected subcutaneously, and 5 times stronger than metoclopramide.

3. Dizziness and migraine after traumatic brain injury. ^[4]

Shubilli contraindications

1. Pregnant women, young children, breastfeeding and pheochromocytoma are forbidden.

2. Disabled in Parkinson's patients. ^[4]

Shubi method dosage

1. Treatment of psychiatric disorders: Start oral administration of 200 mg per day, 2 to 3 times a day, then increase 200 mg every two days until 300 to 800 mg per day, 2 to 3 times a day, the highest dosage is 1600 mg per day; intramuscular injection begins 200 mg per day, 2 to 3 injections can be increased to 600mg per day. Can also be infused 300mg per day, added to 5% glucose injection, slowly infused, can be increased to 600mg per day in the future. For drug refusal or treatment, it can be administered by injection within 1 to 2 weeks, and then changed to oral.

2. For antiemetics: 600 to 1200mg per day can be taken orally in divided doses.

3. For peptic ulcer: 100 to 300 mg per day, divided into 3 to 4 doses.

4. For migraine: 100 ~ 200mg daily, divided into doses. ^[4]

Sulpiride adverse reactions

1. Common insomnia, early awakening, headache, irritability, fatigue, loss of appetite and so on. There are anticholinergic adverse reactions such as dry mouth, blurred vision, tachycardia, dysuria and constipation.

2. Extrapyramidal reactions such as tremor, stiffness, salivation, bradykinesia, inability to sit still, and acute dystonia can occur at doses greater than 600 mg (6 tablets) a day.

3. Most cause increased prolactin concentrations in the plasma. Possible symptoms are: galactorrhea, male feminized breasts, menstrual disorders, amenorrhea, and weight gain.

4. Electrocardiogram abnormalities and liver damage may occur.

5. A small number of patients may experience excitement, agitation, sleep disturbances, or elevated blood pressure.

6. Long-term heavy medication can cause tardive dyskinesia. ^[4]

Precautions

1. (1) patients with hypertension; (2) patients with severe cardiovascular disease and hypotension; (3) patients with liver and kidney dysfunction; (4) pregnant women; (5) patients with mild mania; (6) patients with epilepsy; (7) Hyperthyroidism; (8) Patients with lung disease; (9) Urinary retention; (10) Those who are allergic to other benzamide antipsychotics.

2. Effects of drugs on children: The safety of newborns is uncertain.

3. The effects of drugs on the elderly: the elderly take sulpiride and the risk of adverse reactions increases.

4. The impact of drugs on pregnancy: the safety of pregnant women has not been determined.

5. The effects of drugs on breastfeeding: it is not clear.

6. Check or monitor before, after and during medication: liver and kidney function and blood image should be checked regularly.

7. Do not engage in dangerous activities such as driving and mechanical operation during the medication.

8. May be taken with food, water and milk to avoid stomach irritation.

9. In the treatment of schizophrenia, oral administration is the main method. For those who refuse to take medicine or can be administered by injection within 1 to 2 weeks after the treatment, it should be changed to oral administration.

10. Sedation and extrapyramidal symptoms can be reduced by reducing the dose or combining anti-parkinsonian drugs.

11. If allergic reactions such as rash and pruritus occur during medication, the drug should be discontinued.

12. Sulpiride can cover the symptoms of vomiting caused by tumors, intestinal obstruction and drug poisoning.

13. Do not stop the medicine suddenly, otherwise it may cause nausea, vomiting, stomach irritation, headache, rapid heartbeat, insomnia, tremor or worsening of the condition. It should be gradually reduced. ^[4]

Medication for pregnant women and lactating women:

Pregnant women should be used with caution and the dose should be reduced. Breastfeeding women should stop breastfeeding while using this product.

Shu Bi Li medication for children:

Children over 6 years of age are converted into adult doses, starting with small doses and slowly increasing the dose.

Shu Bi Li medication for the elderly:

Elderly patients should start with small doses and slowly increase the dose. ^[5]

Sulpiride drug interactions

Combination with central nervous system inhibitors or tricyclic antidepressants can cause excessive sleepiness. Combined with tramadol and zotepine can increase the risk of seizures. Lithium can aggravate the adverse reactions of this product and reduce its efficacy. When sucralfate is used, the bioavailability of this product is reduced by 40%. Antacids and antidiarrheals can reduce the absorption rate of this product, and the two should be used at least 1 hour apart. ^[5]

Sulpiride

Sulpiride (thiobenzamide, suning, antipyrene, antipyrene) is a benzoamide antipsychotic. It has the effect of mental stability and emotional activation, and has a strong antiemetic effect, which is 100 times stronger than chlorpromazine. And has a strong anti-stiffening, shrinking, hallucinations, delusions, insanity and certain antidepressant effects. No sedative and hypnotic effect. This product is well absorbed orally, the plasma protein binding rate is <40%, and the half-life is 6-9 hours. For the treatment of schizophrenia include hallucinations, depression, hallucinations caused by levodopa or compound levodopa and other psychiatric symptoms, tics-Tourette syndrome. The dose was increased from 25mg / time, 2 ~ 3 / d to the optimal dose, and rarely produced extrapyramidal reactions.

Clinical manifestations of Sulpiride

1. Excitement, sleep disturbance, thirst, and occasional gastrointestinal reactions occur early in the medication.

2. Large-dose application can cause extrapyramidal reactions, endocrine disorders such as menstrual disorders, lactation, male breast development, impotence, etc. Increased doses too quickly may be transient ECG changes, high blood pressure or orthostatic hypotension, and chest tightness with a rapid pulse.

3. Allergic reactions such as rash and itching can occur.

Shubili diagnosis

The main points of diagnosis of Shubili poisoning are:

1. There is a history of taking or accidentally taking sulpiride, and the above clinical manifestations appear.

2. Eliminate the possibility of poisoning by other drugs.

Sulpiride treatment

The main points of treatment of sulpiride poisoning are:

1. Oral overdose should promptly induce vomiting, gastric lavage and swallowing medicinal charcoal.

2. This medicine is taken orally in excess, and there is no specific antidote. It is mainly symptomatic supportive treatment, such as the treatment of hypertension or hypotension, extrapyramidal reactions and so on.

3. When an allergic reaction occurs, the drug should be stopped immediately and anti-allergic treatment should be given. ^[6]

Shu Bi Li expert review

Has a strong antipsychotic effect. It has strong anti-stiffness, shrinking, hallucinations, delusions and insanity, and has a certain anti-depressant effect. There is no hypnotic effect, and it does not affect the normal activities of people after medication. In addition, it has a strong antiemetic effect. Oral is 160 times stronger than chlorpromazine. ^[4]