What Is Levamisole?

Levamisole (levamisole) is obtained by racemic tetraimidazole and d-camphor-10-sulfonic acid ring, and then hydrolyzed to a salt. Or DL-tetraimidazole is resolved by neutralization with caustic soda to obtain L-tetraimidazole, which is finally obtained as a salt. Levamisole (levamisole) is a broad-spectrum intestinal anthelmintic, mainly used to drive roundworms and hookworms.

Drug Name: Levamisole
Foreign name: levamisole
Whether prescription drugs: prescription

Main indications: Used to drive roundworms and hookworms
Dosage form: tablet
Whether to include health insurance: Incorporate

Brief introduction of levamisole compound

Chinese name: levamisole

Chinese alias: Baosongti; L-imidazole base; Exotropium; L-tetramisole hydrochloride; L-imidazole; L-metridium hydrochloride; L-thiaimidazole; L-imidazole hydrochloride

English name: levamisole

English alias: l-tetramisole; LEVAMISOLE BASE; Levamisole; Ketrax; lepuron

CAS number: 14769-73-4

Molecular formula: C ₁₁ H ₁₂ N ₂ S

Structural formula:

Molecular weight: 204.29100

Exact mass: 204.07200

PSA: 40.90000

LogP: 1.51960

Physical and chemical properties

Appearance and properties: white to off-white crystalline powder

Density: 1.32g / cm ³

Melting point: 230-233ºC

Boiling point: 344.4ºC at 760mmHg

Flash point: 162.1ºC

Storage conditions: 0-6ºC

Vapor pressure: 6.61E-05mmHg at 25 ° C

Security Information

Customs code: 2934999090

Dangerous Goods Transport Code: UN 2811 ^[1]

Levamisole Drug Description

Pharmacological effects of levamisole

Can inhibit the succinate dehydrogenase activity of the parasite muscle, causing the muscle to contract and paralyze continuously.

Levamisole indications

Is a broad-spectrum intestinal worm medicine, mainly used for worms and hookworms. This product can improve patients' resistance to bacterial and viral infections. It is currently being tested as an adjuvant therapy for lung cancer, breast cancer surgery, or after chemotherapy for acute leukemia or worsening lymphoma. In addition, it can also be used for autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and upper sensation, respiratory infections in children, hepatitis, fungal scabs, sores, abscesses, etc. Preliminary trials of refractory bronchial asthma have been shown to have significant short-term effects.

Dosage of levamisole

Deworming: 100-200mg daily for adults, 1 hour after meal. Children 2-3mg per kilogram of body weight per day

Hookworm : 100-200mg daily, take 1 hour after meal, even for 2-3 days.

Treatment of filariasis : 200-300mg daily, taken 2-3 times after meals, and even for 2-3 days.

Adjuvant treatment of cancer : 150-250mg per day, 3 consecutive servings, 11 days rest, and then the next course of treatment.

Treatment of rheumatoid arthritis, etc . : 50mg each time, 2-3 times daily, can be taken continuously.

Treatment of bronchial asthma : 50mg per serving, 3 times a day, 3 consecutive days, 7 days of withdrawal, 6 months as a course of treatment.

Levamisole precautions

Occasionally dizziness, nausea, vomiting, abdominal pain, loss of appetite, fever, lethargy, fatigue, rash, itching and other adverse reactions, can relieve itself after stopping treatment. Individual patients may have leukopenia, exfoliative dermatitis, and liver damage. Early pregnancy, liver dysfunction and renal dysfunction should be used with caution, and active hepatitis should not be used.

Levamisole specifications

Tablets: hydrochloride, each tablet contains 15mg, 25mg, 50mg of matrix.

Levamisole adverse reactions

Levamisole contraindications

Early pregnancy, liver dysfunction and renal dysfunction should be used with caution, and active hepatitis should not be used.

Related studies of levamisole

Pharmacological research

To explore the effect of levamisole on the prevention of Schistosoma japonicum cercariae infection. Methods The oral doses of levamisole hydrochloride and levamisole base were 26.25 mg / kg, which were taken orally 2 days before the infection in mice, and even taken for 7 days, and the skin preparation was 1.0%, 2.0%, 3.0%, 5.0% and 7.0% were applied on the day before, and on the day of infection. The body was dissected 4 weeks after stopping the drug, and the worm body was detected. Results The levamisole hydrochloride aqueous solution and the levamisole base aqueous solution were taken orally respectively, and the worm reduction rate was 0; 5.0% levamisole hydrochloride was applied to the skin on the day of infection, and 7.0% levamisole hydrochloride was applied to the skin one day before the infection to reduce worms. The rates were 100.0%; 2.0%, 3.0%, and 5.0% of levamisole were applied on the day before infection, and the deworming rate was 100.0%. Conclusion The levamisole coating can prevent the infection of Schistosoma japonicum cercariae. The effect of levamisole base is better than that of levamisole hydrochloride.

To observe the effects of levamisole (LMS) on the expression of CD4, CD28 and CD152 on mononuclear cells in the spinal cord of experimental allergic encephalomyelitis (EAE) rats, and to explore the pathogenesis of inflammatory demyelinating white matter encephalopathy induced by LMS. Methods The expression levels of CD4, CD28 and CD152 on mononuclear cells of spinal cord of EAE rats were detected by flow cytometry. Results The expression levels of CD4 and CD28 on mononuclear cells in the spinal cord of rats in the LMS simultaneous administration group and the pretreated EAE group were significantly higher than those in the non-LMS treated EAE model group. Conclusion LMS can promote the expression of CD4 and CD28 on mononuclear cells in the spinal cord of EAE rats, suggesting that LMS up-regulates the expression of CD4 and CD28 and may be associated with inflammatory demyelinating leukoencephalopathy induced by LMS.

The effect of levamisole on the cellular and humoral immune function of chicken was studied. The results show that levamisole can affect the immune function of normal chickens: levamisole can significantly promote the proliferation of T lymphocytes in chicken peripheral blood, but has no significant effect on B lymphocytes: 2.5210mg / kg levamisole can make CD4 ^ + / CD8 ^ + Lymphocyte ratio was significantly increased; levamisole could increase anti-granularity, thymus-dependent antigen SRBC antibody titer, anti-solubility, thymus-dependent antigen BSA antibody titer and anti-non-thymus-dependent antigen BA antibody titer in chickens Are significantly increased;

Observe MMP-1, MIP-1 , MMP- in the blood-brain barrier (BBB) and central nervous system (CNS) of experimental allergic encephalomyelitis (EAE) rats administered at different stages of levamisole (LMS) The effects of 2 and ICAM-1 expression provide experimental basis for explaining the pathogenesis of LMS leukoencephalopathy. Methods: 45 female wistar rats were divided into 5 groups: CFA control group, model (EAE) group, and LMS pre-immunization group (LMS1), LMS immunization simultaneous administration group (LMS2), LMS immunization intermittent administration group (LMS3). Subcutaneous injection of guinea pig spinal cord homogenate with complete Freund's adjuvant (GPSCH-CFA) antigen emulsion EAE model was established in mice. LMS1 was given to LMS (10mg / kg, ip, bid × 7d) before immunization, LMS2 was given to LMS (10mg / kg, ip, qd × 3d) at 0, 24h, and 48h, and LMS3 was given after immunization. LMS (10mg / kg, ip, qd × 3d) was given every 11 days for a total of 6 times. The CFA control group and EAE group were injected intraperitoneally with physiological saline (NS) instead. The day of immunization was set to day 0. Daily observation and Changes in animal behavior and body weight were recorded. Animals in each group were sacrificed at the peak of onset (half of the animals in the CFA control group and LMS3 were treated at the peak of relapse ), Take the brain and spinal cord, fix with paraformaldehyde, perform HE staining and Kluver & Barrera myelin staining. Immunohistochemical method (SABC method) to measure the expression of GFAP, IgG, MCP-1, MIP-1 ; in situ hybridization The number of cells expressing MCP-1, MMP-2, and ICAM-1 mRNA was determined. Results: Behavioral observation: The earliest onset in the EAE group was on the 13th day (13dpi) after immunization, with an incubation period of 13.67 ± 1.15dpi. Reduced activity, reduced food intake, and weight loss. First, there was a decrease in tail tension, tail mopping and failure to lift the floor, followed by weakness in hind limbs, abnormal gait, and paralysis. The incubation periods of the LMS1 and LS2 groups were 14.40 ± 2.07dpi and 14.00 ± 1.19dpi, respectively. There was no significant difference in the EAE group. At 14 dpi, the average clinical symptom scores of the LMS1 and LMS2 groups (2.50 ± 0.71, 2.00 ± 0.00) were significantly higher than the EAE group (1.00 ± 0.00) (P <0.01, P <0.05). LMS1 The mean maximum symptom score (3.80 ± 0.45) in the group was higher than that in the EAE group (P <0.05). The incidence of the LMS2 group (8/9) was higher than that in the EAE group (3/8) (P <0.05). L, MS3 group Rats developed onset at 14.00 ± 1.37 dpi, and 2/10 rats relapsed at 24.00 ± 1.41 dpi. CFA control rats on day 14 though Adjuvant arthritis symptoms, swelling of both hind limbs, staggering symptoms, but no signs of neurological damage such as tail weakness, sagging, paralysis and hind limb weakness, paralysis. Pathological changes: different degrees can be seen in the CNS of the EAE group Infiltration of inflammatory cells, most prominent in the brainstem and spinal cord, is mainly manifested by vascular sheath formation, neurophagic phenomena: swelling, degeneration, and necrosis of nerve cells. Kluver & Barrera myelin staining found extensive degeneration and loss of nerve myelin sheaths. The brainstem, spinal cord, and cerebellum are the same, but the axons are relatively intact. The CNS inflammatory infiltration and demyelination of the rats in the LMS1 and LMS2 groups tend to increase. The LMS3 group has inflammatory infiltration and demyelinating changes during the relapse period. CFA control No inflammatory cell infiltration and demyelination were observed in the rats in the group. Immunohistochemical results: Compared with the CFA control group, the expression of GFAP and IgG in the CNS of the EAE group was significantly increased. Compared with the EAE group, LMS1 The expression of GFAP and IgG in the LMS2 group was significantly increased; in the relapse period, the expression of GFAP and IgG was seen in the LMS3 group. Compared with the CFA control group, the expression of MCP-1 and MIP-1 in the CNS of the EAE group increased. Compared with the EAE group, Phase, the expression of MCP-1 in CNS of LMS1 and LMS2 rats increased significantly (P <0.01): MIP-1 in brainstem of LMS1 rats increased significantly (P <0.01), and the waist of rats in LMS1 and LMS2 groups increased significantly. Myeloid MIP-1 increased (P <0.05). During the relapse period, the expression of MCP-1 and MIP-1 in CNS of LMS3 group rats. In situ hybridization results: Compared with CFA control group, EAE group rats in CNS MCP-1, MMP-2, and ICAM-1 mRNA-positive cells increased in number, and were significantly expressed in the cerebral cortex and brain stem. Compared with the EAE group, MCP-1, MMP-2, and ICAM were expressed in the brains of rats in the LMS1 and LMS2 groups. The number of -1mRNA positive cells staining increased (P <0.01). The expression of MCP-1, MIdP-2, and ICAM-1mRNA positive cells was seen in the LMS3 group during the relapse period. Conclusion: LMS pre-immunization can aggravate the clinical symptoms of EAE in Wistar rats , Accelerate disease progression, increase inflammation infiltration and demyelination. Simultaneous administration of LMS immunization can increase the incidence of EAE in Wistar rats, and aggravate clinical symptoms, accelerate disease progression, increase inflammation infiltration and demyelination. After LMS immunization Phased administration can lead to the recurrence of EAE in Wistar rats. BBBB permeability increases during the course of LMS-induced EAE. In LMS-induced EAE Activated astrocytes. LMS EAE rats increased BBB permeability may be related to MCP-1, MIP-1 , MMP-2 and ICAM-1 upregulation, and thus mediate T lymphocytes into the CNS from the outer periphery ^[2] .

Pharmacokinetic research

Analysis of the thermal decomposition process of solid thiazole anthelmintic drug levamisole. Thermogravimetric analysis and differential scanning calorimetry were used to study the thermal decomposition kinetics of the drug levamisole, and the thermal decomposition kinetic parameters E, A, and were calculated; combined with quantum chemistry, the bond lengths and atoms of organic structures The electrostatic charge was used to study the thermal decomposition mechanism, and the thermal decomposition mechanism and products and storage period were deduced. The thermal analysis method of solid drug levamisole was simple and reliable, and the results were reliable ^[2] .

Clinical research

theme

To study the clinical and CT and MRI diagnostic value of levamisole-induced demyelinating encephalopathy.

method

The clinical data of 26 cases of levamisole-induced demyelinating encephalopathy, 18 cases of CT, and 20 cases of MRI were analyzed.

result

The main clinical manifestations of this disease are diffuse brain damage with acute or subacute onset. One brain biopsy revealed a demyelinating lesion. Corticosteroids work well. Thirteen cases of CT and 20 cases of MRI showed multiple lesions in the white matter area of the brain. CT was a low-density image, and MRI was a long T1 long T2 signal. Only one case had a placeholder effect. The imaging diagnosis rate of MRI is significantly higher than that of CT. Conclusion: The diagnosis of this disease depends on its clinical characteristics and imaging examination. The diagnostic value of MRI is significantly better than that of CT ^[2] .