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Metoclopramide: An Antiemetic in Chemotherapy Induced Nausea and Vomiting

Mini Review | Open Access

  • 1. Department of Oncology, Odense University Hospital, Denmark
  • 2. Department of Oncology, Odense University Hospital and the University of Southern Denmark, Denmark
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Corresponding Authors
Jørn Herrstedt, Department of Oncology, Odense University Hospital, DK-5000, Odense C, Denmark Tel: 45-6541-3634
Abstract

Chemotherapy induced nausea and vomiting (CINV) are two of the most feared adverse events experienced by cancer patients undergoing chemotherapy. Metoclopramide was derived from procainamide in the 1950s and one of the first drugs investigated in the prophylaxis of nausea and vomiting induced by chemotherapy. The breakthrough came in 1981 with the recognition that high-dose metoclopramide was effective and tolerable in the prevention of cisplatin-induced nausea and vomiting. A combination of high- dose metoclopramide and a corticosteroid was the standard antiemetic recommendation until the serotonin (5-HT)3 -receptor antagonists, ondansetron, granisetron, tropisetron and dolasetron became available in the beginning of the 1990s.

The development of these highly selective (5-HT)3 -receptor antagonists with a superior effect and a preferable tolerability profile has limited the use of metoclopramide to be prescribed as a rescue antiemetic, when guideline recommended antiemetic therapy fails.

Keywords

Keywords • Metoclopramide • Chemotherapy • Nausea • Vomiting • Emesis

ABBREVIATIONS

CINV: Chemotherapy-Induced Nausea and Vomiting; MCP: Metoclopramide; NK1 -Receptor Antagonist: Neurokinin (NK)1 -Receptor Antagonist; 5-HT3 -Receptor Antagonist: 5-Hydroxytryptamine (5-HT)3 -Receptor Antagonist

 

INTRODUCTION

Metoclopramide (MCP) is a dopamine receptor antagonist, and is the most intensively investigated drug of this class as regards prophylaxis of chemotherapy-induced nausea and vomiting (CINV).

MCP (2-methoxy-5-chloro-procainamide) was originated in the 1950s as a substituted benzamide derived from procainamide a drug with local anesthetic and antiarrhythmic properties [1]. In therapeutic doses, MCP is almost devoid of these effects, but instead enhances gastrointestinal motility and possesses antiemetic effect.

MCP was tested in the early 1960s by Justin-Besancon, Laville, and Thominet [2] and soon proved to be effective against nausea and vomiting induced by a number of non-malignant conditions such as dyspepsia, delayed gastric emptying and postoperative nausea and vomiting [1,3].

The emetic risk of chemotherapy is divided in high emetic risk (risk of vomiting 0-24 hours after chemotherapy > 90%), moderate emetic risk (30-90%), low emetic risk (10-30%) and minimal emetic risk (< 10%). This paper will review studies with MCP in the prophylaxis of nausea and vomiting in patients receiving high and moderate emetic risk chemotherapy, primarily cisplatin (high risk), anthracyclines (moderate risk), cyclophosphamide (moderate risk) and the combination of an anthracycline and cyclophosphamide (high risk). The most important randomized studies are summarized in Table 1.

The early trials (1960-1989)

Conventional, low doses of MCP: In randomized, doubleblind trials, oral doses of MCP 20 mg x 2-3 were equal to placebo or to prochlorperazine, (but both were ineffective) and inferior to dexamethasone or domperidone against nausea and vomiting induced by both non-cisplatin-based and cisplatin-based chemotherapy [4-7]. It should be noticed, that in these early trials, only the first 24 hours after chemotherapy was evaluated, and it can therefore be concluded, that MCP in oral doses up to 20 mg is no better than placebo in the period 0-24 hours after chemotherapy. The interest in investigating MCP in conventional doses was therefore modest during the 1960s and 1970s.

 

Table 1: Important randomized studies 1960-2017 in the development of metoclopramide as an antiemetic in the prophylaxis of CINV

Reference Number of patients Chemotherapy Investigational Arm Comparator Primary parameter Results*
Moertel et al. 1969 [4], 144 Non-CIS MCP 20 mg x 3 po PLA MPZ 5 mg x 3 po Incidence of nausea and vomiting days 1-4 MCP = MPZ = PLA
Frytak et al. 1981 [6], 100 CIS MCP 20 mg x 3 po PCP Vomiting MCP > PCP, both ineffective
Gralla et al. 1981[8], 41 CIS MCP 2 mg/kg x 5 iv PLA PCP 10 mg x 5 im Number of EE 0-24 hours MCP > PLA MCP > PCP
Grunberg et al. 1984 [19], 28 CIS MCP 2 mg/kg x 5 iv HAL 3 mg/kg x 5 iv Number of EE 0-24 hours MCP > HAL
Kris et al. 1985 [9], 60(24 received 3 mg/kg x 2 CIS MCP 2 mg/kg x 5 iv MCP 3 mg/kg x 2 iv Number of EE 0-24 hours 3 mg/kg x 2 iv = 2 mg/ kg x 5 iv
Warrington et al. 1986 [11], 33 CIS MCP 7 mg/kg divided in 5 bolus infusions + DEX 20 mg iv MCP 3 mg/kg followed by 4 mg/kg (8 hour continuous infusion) + DEX 20 mg iv Nausea and vomiting 0-24 hours Nausea, vomiting and patient preference in favor of the continuous regimen
Kris et al. 1987 [22] 120 CIS MCP 3mg/kg x 2 iv + DEX 20 mg iv + DPH 50 mg iv MCP 3mg/kg x 2 iv + DEX 20 mg iv + L 1.5 mg/m2 iv Number of EE 0-24 hours Safety No difference in EE, but less restlessness with L
Roila et al. 1989 [10], 367 CIS MCP 1 mg/kg x 4 iv + MP 250mg x 2 iv MCP 3 mg/kg x 2 iv + DEX 20 mg iv + DPH 50 iv Complete protection from vomiting/nausea 0-24 hours, Safety MCP 3 mg/kg superior as concerns EE, nausea and safety (
Marty et al. 1990 [33] 97 CIS OND 8 mg iv + OND 1 mg/h iv for 24 hours MCP 3 mg/kg iv + MCP 0.5 mg/kg/h for 8 hours Number of patients with 0-2 EE 0-24h OND > MCP
De Mulder et al. 1990 [34], 125 CIS OND 8 mg iv + OND 1 mg/h iv for 24 hours + OND 8 mg x 3 po days 2-6 MCP 3 mg/kg iv + MCP 0.5 mg/kg/h for 8 hours+ MCP 20 mg x 3 po days 2-6 Number of patients with 0-2 EE 0-24 h Number of patients with 0-2 EE days 2-6 0-24 h: OND > MCP Day 2-6: Vomiting: OND = MCP Nausea:Ond
Bonneterre et al. 1990 [39], 75 FAC or FEC OND 4 mg iv + OND 4 mg po day 1 + OND 8 mg x 3 po for 3-5 days MCP 60 mg iv + MCP 20 mg po day 1 + MCP 20 mg x 3 po for 3-5 days Number with 0-2 EE (day 1) Number with 0-2 EE (days 2-3) EE: OND > MCP (days 1-3) Nausea: OND > MCP (day 1) Nausea: OND = MCP (days 2-3)
Kaasa et al. 1990 [40], 93 AC or EC OND 8 mg iv day 1 + OND 8 mg x 3 po for 3-5 days MCP 60 mg iv + MCP 20 mg po x 3 for 3-5 days EE (day 1) but not specified if the primary parameter was number with 0 EE or with 0-2 EE. EE (days 2-3) same comment 0 EE: OND > MCP (day 1) 0 EE: OND = MCP (days 2-3) Nausea: OND > MCP (day 1) Nausea: OND = MCP (days 2-3)
Marschner et al. 1991[41], 122 EC or FEC OND 8 mg po + OND 8 mg x 3 po for 3-5 days MCP 60 mg iv + MCP 20 mg po x 3 for 3-5 days Number of patients with 0-2 EE 0-24 h. OND = MCP
Warr et al. 1993 [35] 151 CIS GRA 80 μg/kg iv MCP 2 mg/kg x 5 iv+ DEX 10 mg iv + DPH10 mg iv Mean nausea score (day 1) Number of patients with 0 EE (day 1) GRA = DEX + MCP + DPH
Chevallier et al.1993 [36], 281 CIS GRA 40 μg/kg iv +up to 2 more doses of GRA if breakthrough emesis within the first 24h MCP 3 mg/kg iv + MCP 0.5 mg/kg/h for 8 hours + DEX 12 mg iv Number of patients with no vomiting and no or only mild nausea 0-24 h GRA = DEX + MCP
Roila et al. 2015 [52], 303 of 480 planned CIS PAL 0.25 mg iv + DEX 12 mg iv + APR 125 mg x 1 po day 1+ DEX 8 mg x 1podays 2-4 + MCP 20 mg x 4 po days 2-4 PAL 0.25 mg iv + DEX 12 mg iv + APR 125 mg x 1 po day 1+DEX 8 mg x 1 po days 2-4+ APR80 mg x 1 podays 2-3 Complete response (no EE and no rescue antiemetics) days 2-5 MCP + DEX = APR + DEX

*> means a statistical significant difference; = means no statistical significant difference, but numerical differences may appear.

0-24 hours means from start of cisplatin infusion until 24 hours after. EE, emetic episodes; AE, adverse events; PCP, prochlorperazine; MCP, metoclopramide; DOM, domperidone; MPZ, metopimazine; DEX, dexamethasone; MP, methylprednisolone; DPH, diphenhydramine; L, lorazepam; HAL, haloperidol; OND, ondansetron; GRA, granisetron; PAL, palonosetron; PLA, placebo; APR, aprepitant; CIS, cisplatin; F, 5-fluorouracil; A, doxorubicin; E, epirubicin; C, cyclophosphamide.

 

High-dose MCP: Gralla and coworkers were some of the first to investigate the effect of high-dose MCP in prevention of cisplatin-induced nausea and vomiting [8]. Their study, published in 1981, actually consisted of two double-blinded randomized trials, the first comparing high-dose MCP to placebo (n = 21) and the second a comparison with prochlorperazine (n = 20). The dose of MCP was 2 mg/kg intravenously administered 5 times, starting 30 minutes before chemotherapy and ending 8.5 hours following cisplatin-based (120 mg/m2 ) chemotherapy, yielding a total dose of MCP10 mg/kg. The primary parameter was the number of emetic episodes within the first 24 hours following cisplatin. Patients receiving MCP had significantly fewer episodes of emesis than patients receiving placebo (median number of emetic episodes 1.0 versus 10.5, p = 0.001) or prochlorperazine (median 1.5 versus 12.0, p = 0.005). MCP also significantly reduced the volume of emesis and shortened the duration of nausea. Adverse events included mild sedation in 76 % of patients receiving MCP versus 50%/40% of patients receiving placebo/prochlorperazine, and one patient in the MCP group experienced an extrapyramidal reaction. This study is the most important one investigating the effect of MCP in CINV, because it was now possible for the first time to prevent nausea and vomiting in cisplatin-treated patients.:

Subsequent studies tried to fine-tune the high-dose MCP regimen, by comparing 4-5 bolus doses of MCP 1-2 mg/kg with two bolus doses of 3 mg/kg [9,10] or with a bolus dose followed by continuous infusion of MCP [11]. Some of these studies also investigated if the antiemetic effect of MCP was correlated to the plasma concentration of MCP [11-16], but inconsistent results were obtained and no clear-cut plasma level was defined.

High-dose MCP was also investigated in non-cisplatin chemotherapy [17], but never obtained the same success as in cisplatin-based chemotherapy. Other dopamine receptor antagonists such as prochlorperazine [18] and haloperidol [19] were investigated in high doses and compared with high-dose MCP, but no advantages with any of these agents were observed.

High-dose MCP combined with a corticosteroid: Even though high-dose MCP was considered the golden standard of antiemetic treatment for patients receiving cisplatin-based chemotherapy, the treatment only prevented nausea and vomiting in about 30-40% of the patients [20]. In 1984-1987 a number of studies demonstrated that the addition of either methylprednisolone [21,22] or dexamethasone [23,24] improved the effect of MCP and in the same time reduced MCP induced adverse events, in particular diarrhea.

High-dose MCP combined with a corticosteroid and diphenhydramine or lorazepam: Acute dystonic reactions induced by high-dose MCP are a significant problem, particularly in younger patients [25,26]. It was soon verified that the addition of diphenhydramine or lorazepam resulted in a significant reduced incidence of extrapyramidal adverse effects. A modified highdose MCP regimen (3 mg/kg x 2 i.v. or 4 mg/kg x 1 i.v.) combined with dexamethasone and lorazepam or diphenhydramine (to decrease the incidence of extrapyramidal adverse effects) was the standard regimen in cisplatin–based chemotherapy [10,27] until the serotonin receptor antagonists became available in the early 1990s.

The later trials (1990-1999)

High-dose MCP versus a serotonin-receptor antagonist: Studies published 1978-1986 demonstrated that the effect of high-dose MCP is not due to antagonism at dopamine receptors, but is caused by antagonism at 5-HT3 receptors [28-31]. This recognition led to the development of a new class of antiemetic agents - the serotonin receptor antagonists of which the first clinical study was published in 1987 [32].

In 1990 two randomized double-blind studies in patients receiving cisplatin-based chemotherapy used a cross over design and compared the antiemetic effect of the serotonin receptor antagonist, ondansetron, with high dose MCP [33,34]. In the first [33] study (n = 97), ondansetron was more effective than MCP in the prevention of acute (0-24 hours) nausea and vomiting and more patients preferred the ondansetron regimen (55% versus 26%, p = 0.006). The second [34] study (n = 125) also found that ondansetron was superior to MCP in the first 24 hours after cisplatin and more patients preferred ondansetron (54% versus 30%, p = 0.012), but MCP was actually more effective in the prevention of delayed nausea (days 2-6, p = 0.016). Also other 5-HT3 -receptor antagonists, such as granisetron [35, 36], tropisetron [37] and dolasetron [38] were compared to either MCP alone [38] or a combination of MCP and dexamethasone [35-37] in patients treated with cisplatin. The conclusion from these studies is that the 5-HT3 -receptor antagonist was superior to single agent MCP [38] and non-inferior to the combination of MCP and dexamethasone [35-37].

Three randomized, double-blind studies published 1990- 1991 compared MCP and ondansetron in patients receiving anthracycline-cyclophosphamide (AC)-based chemotherapy [39- 41]. The AC combination was in 1990 classified as moderately emetogenic, but is today recognized as highly emetogenic [42]. In two studies including a total of 178 evaluable patients [39,41], all were women with breast cancer, and in the third study [39] the majority (n = 51) were women with breast cancer as well, but also patients with non-Hodgkin’s lymphoma (n = 31) and other tumor types (n = 11) were included. In two trials, ondansetron was significantly superior to MCP as concerns acute (0-24 hours) vomiting and nausea [39,40] and ondansetron was in one of these studies [39] also significantly superior in the prevention of vomiting (but not nausea) days 2-3. In the third trial [41] no statistical significant differences were seen.

These studies led to a shift in standard antiemetic therapy for both cisplatin-based and AC-based chemotherapy. A 5-HT3 - receptor antagonist was now recommended instead of MCP and subsequent studies demonstrated the advantage of combining a 5-HT3 -receptor antagonist with dexamethasone [43] and this combination was the golden standard until the first NK1 -receptor antagonist, aprepitant, became available in 2003.

MCP in the prevention of delayed nausea and vomiting: Until the mid-1980s, the vast majority of antiemetic studies evaluated patients during the first 24 hours after chemotherapy, only. Kris et al., extended the observation time to include the period from 24-120 hours after cisplatin-based chemotherapy and antiemetic prophylaxis with high-dose MCP (3 mg/kg x 2 i.v.) plus dexamethasone 20 mg i.v. combined with either diphenhydramine or lorazepam to avoid extrapyramidal adverse reactions from MCP [44]. Patients received a prescription for oral prochlorperazine to be taken in case of delayed symptoms, but no routine antiemetics were prescribed. Although 63% of the patients did not vomit in the first 24 hours, both vomiting and nausea were frequently reported 24-120 hours after cisplatin, and particular day 3 (48-72 hours) were troublesome with 78% and 61% suffering from delayed nausea and vomiting, respectively [44]. In a subsequent trial, the same group randomized patients treated with high-dose cisplatin to delayed antiemetic prophylaxis with placebo, dexamethasone alone or dexamethasone plus MCP and found that the combination was superior to placebo and to dexamethasone alone [45]. Subsequent studies have confirmed the effect of this combination in the prophylaxis of delayed nausea and vomiting [46,47].

The newest trials and the evidence-based guidelines (2000-2017)

The first clinical trial with an NK1 -receptor antagonist was published in 1997 [48]. Today three agents of this drug class have been marketed, namely aprepitant, rolapitant and netupitant (given as NEPA in combination with the 5-HT3 -receptor antagonist, palonosetron). The recent interest in investigating MCP has been modest, because the 5-HT3 -receptor antagonists are superior with a more preferable adverse event profile. Therefore evidence-based guidelines of today do not recommend MCP (or other dopamine receptor antagonists) for routine use. MCP is therefore primarily recommended as a rescue antiemetic, when routine antiemetic therapy fails [42,43].

There are a few exceptions from the above statement. MCP is recommended (equally with dexamethasone or a 5-HT3 -receptor antagonist) in the prophylaxis of acute nausea and vomiting induced by chemotherapy with a low emetogenic potential [49]. Also MCP is recommended in the treatment of nausea and vomiting not induced by chemotherapy in patients with advanced cancer [50] and as prophylaxis or rescue in patients receiving radiotherapy of a low or minimal emetogenic potential [51], but none of these indications are within the scope of this review.

A recent study re-addressed the potential use of MCP as part of an antiemetic combination in the prophylaxis of delayed nausea and vomiting following cisplatin-based (≥ 50 mg/m2 ) chemotherapy. In a randomized, double-blind study in which all patients (n = 303) received the same antiemetic prophylaxis for acute nausea and vomiting, patients were randomized to either dexamethasone plus aprepitant or to dexamethasone plus metoclopramide for delayed emesis protection [52]. Both combinations were equally effective in the prevention of delayed nausea and vomiting, and current guidelines therefore recommend the use of dexamethasone combined with either MCP or aprepitant in patients receiving non-AC highly emetogenic chemotherapy and aprepitant, a 5-HT3 -receptor antagonist and dexamethasone for acute CINV prophylaxis [42]. If another NK1 -receptor antagonist (rolapitant or netupitant) is used for prophylaxis day 1, dexamethasone alone is recommended [42].

Safety of metoclopramide: Common side-effects (≥ 1 % of patients) include somnolence, diarrhea, hypotension, akathisia, dry mouth, depression, fatigue and extrapyramidal symptoms [25,26] which can all be dose limiting. As previously mentioned, the addition of diphenhydramine or lorazepam to high-dose metoclopramide decreases the risk of extrapyramidal symptoms [10,26,27]. Metoclopramide must be used with caution in younger female patients in whom the risk of neurological sideeffects is particularly high [53].

Both The European Medicines Agency (EMA) and The Food and Drug Administration (FDA) have advised against long-term use and use of high doses [54,55]. This means that metoclopramide is not to be used for more than five days and in a maximum dose of 10 mg x 3 daily. This is of course a barrier to the use as an antiemetic in CINV.

 

CONCLUSION

Although not originally developed as an antiemetic (contrary to the selective 5-HT3 - and NK1 - receptor antagonist antiemetics), MCP became the first milestone in the prophylaxis of CINV. This was primarily due to the effect of high-dose MCP, which was the first effective regimen in the prevention of cisplatin induced emesis [8], a group of patients previously facing an almost 100% risk of vomiting.

In countries with access to 5-HT3 -receptor antagonists and NK1 -receptor antagonists, MCP is rarely used as a routine antiemetic prophylaxis, but is still important as a rescue antiemetic. The modest pricing of metoclopramide compared to the more modern antiemetics still makes MCP an important resource in low-income countries.

 

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Current Applications of Chitosan and Chito-Oligosaccharides. A Review

Received : 13 Jan 2017
Accepted : 16 Mar 2017
Published : 17 Mar 2017
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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