Hubbry Logo
TofisopamTofisopamMain
Open search
Tofisopam
Community hub
Tofisopam
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Tofisopam
Tofisopam
Tofisopam
View on Wikipedia
from Wikipedia

Tofisopam
Clinical data
Other names6-(3,4-Dimethoxyphenyl)-2-ethyl-9,10-dimethoxy-3-methyl-4,5-diazabicyclo[5.4.0]undeca-3,5,7,9,11-pentaene
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
MetabolismHepatic
Elimination half-life3 hours[1][2]
ExcretionRenal
Identifiers
  • 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.040.823 Edit this at Wikidata
Chemical and physical data
FormulaC22H26N2O4
Molar mass382.460 g·mol−1
3D model (JSmol)
  • O(c3ccc(C\2=N\N=C(/C(c1c/2cc(OC)c(OC)c1)CC)C)cc3OC)C
  • InChI=1S/C22H26N2O4/c1-7-15-13(2)23-24-22(14-8-9-18(25-3)19(10-14)26-4)17-12-21(28-6)20(27-5)11-16(15)17/h8-12,15H,7H2,1-6H3 checkY
  • Key:RUJBDQSFYCKFAA-UHFFFAOYSA-N checkY
  (verify)

Tofisopam[3] (Emandaxin, Grandaxin, Sériel) is an anxiolytic that is marketed in several European countries.[4] Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines (which are generally 1,4- or 1,5-substituted) however, tofisopam does not have anticonvulsant, sedative,[5] skeletal muscle relaxant, motor skill-impairing or amnestic[6] properties. While it may not be an anticonvulsant in and of itself, it has been shown to enhance the anticonvulsant action of classical 1,4-benzodiazepines (such as diazepam) and muscimol, but not sodium valproate, carbamazepine, phenobarbital, or phenytoin.[7][8] Tofisopam is indicated for the treatment of anxiety and alcohol withdrawal, and is prescribed in a dosage of 50–300 mg per day divided into three doses. Peak plasma levels are attained two hours after an oral dose. Tofisopam is not reported as causing dependence to the same extent as other benzodiazepines, but is still recommended to be prescribed for a maximum of 12 weeks.

Tofisopam is not approved for sale in the United States or Canada. However, Vela Pharmaceuticals of New Jersey is developing the D-enantiomer (dextofisopam) as a treatment for irritable bowel syndrome,[9] with moderate efficacy demonstrated in clinical trials so far.[10]

Tofisopam is also claimed to be a PDE10A inhibitor, which may provide an alternative mechanism of action for its various therapeutic effects, and this action has been proposed to make tofisopam potentially useful as a treatment for schizophrenia.[11]

Tofisopam has been shown to act as an inhibitor of the liver enzyme CYP3A4,[12][13] and some researches suspect that this could cause dangerous drug interactions with other medications metabolised by this enzyme,[14][15] although the clinical significance of these findings remains unclear.

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Tofisopam

View on Grokipedia
from Grokipedia
Tofisopam is a 2,3-benzodiazepine derivative used as an atypical medication primarily for the treatment of and alcohol withdrawal symptoms. Unlike classical 1,4-benzodiazepines such as , it lacks , , , and amnestic effects, making it suitable for daytime use without impairing cognitive function or psychomotor performance. It is approved and marketed under brand names like Grandaxin and Emandaxin in several countries, including , , , , , and others in . Pharmacologically, tofisopam exerts its anxiolytic effects through selective inhibition of phosphodiesterase (PDE) isoenzymes, such as PDE-4A1 (IC₅₀ = 0.42 μM) and PDE-10A1 (IC₅₀ = 0.92 μM), which increases intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) without binding to the benzodiazepine site on GABA_A receptors. This unique mechanism contributes to its mild stimulant-like properties and absence of typical benzodiazepine side effects, including dependence liability and withdrawal symptoms observed with drugs like . Clinical studies have demonstrated comparable anxiolytic efficacy to at doses of 50 mg three times daily, but with improved tolerability and no significant impact on quality or daytime alertness. Developed in the , tofisopam has been approved for clinical use since that decade in select regions, with research interest in its potential applications for conditions like (has been investigated in Phase II trials via its D-enantiomer, dextofisopam) and post-COVID-19 neuropsychiatric sequelae (based on a 2021 case series). It is classified under the Anatomical Therapeutic Chemical (ATC) code N05BA23 as an . Despite its long history, it remains unavailable in , where regulatory approval has not been granted.

Medical Uses

Indications

Tofisopam is primarily indicated for the treatment of anxiety disorders, including generalized anxiety, in several countries worldwide, including in (such as and ), (such as and ), and others, where it is marketed under brand names such as Grandaxin and Emandaxin. As a 2,3-benzodiazepine, it provides effects without the , , or amnestic properties commonly associated with traditional 1,4-benzodiazepines. The typical dosage for anxiety ranges from 50 to 300 mg per day, divided into three doses. It is also indicated for the management of alcohol withdrawal symptoms, including agitation and tremors. Treatment for alcohol withdrawal often initiates with lower doses to mitigate symptoms while minimizing risks. The D-enantiomer of tofisopam, known as dextofisopam, has been investigated for potential use in (IBS), particularly diarrhea-predominant or alternating subtypes. In a randomized, -controlled phase 2 involving 140 patients, dextofisopam at 200 mg twice daily demonstrated superior efficacy over for overall symptom relief (P=0.033), with notable improvements in stool consistency in both men and women and reduced stool frequency in women; adverse events were comparable to placebo, supporting its tolerability. This remains an investigational application, with no current approval for IBS treatment. As of 2025, research continues into its potential for other conditions, including post-COVID-19 neuropsychiatric sequelae, though these remain unapproved.

Dosage and Administration

Tofisopam is administered orally in tablet form, typically available in 50 mg strengths, and can be taken with or without food to accommodate patient preferences and minimize gastrointestinal discomfort. The standard dosing regimen for adults is 50–300 mg per day, divided into 2–3 doses, with initial doses often starting at 50–100 mg daily and titrated upward based on clinical response and tolerance. Treatment should be limited to short-term use, with periodic evaluation to determine the need for continuation and to minimize any potential risks. The last daily dose is preferably taken before 5 p.m. to avoid potential sleep disturbances. In special populations, dosing adjustments are recommended to enhance safety. For elderly patients, who may exhibit increased sensitivity to effects, a lower starting dose (e.g., 50 mg daily) is advised, with careful . Patients with hepatic impairment require reduced dosing or cautious use due to potential accumulation and heightened risk of adverse effects, starting at the lower end of the range and monitoring closely. Regular monitoring is essential throughout treatment, including assessments of therapeutic efficacy, such as symptom improvement in anxiety, and safety parameters like or cognitive changes, to guide dose adjustments or discontinuation.

Adverse Effects and Safety

Side Effects

Tofisopam is generally well-tolerated, with a profile that is milder than that of traditional 1,4-benzodiazepines, lacking significant , muscle relaxation, or amnestic effects. In clinical trials, adverse events associated with tofisopam occurred at rates similar to , ranging from approximately 1.6% to 21% of patients, depending on the study population and duration, and most were transient and mild. Common side effects primarily involve mild gastrointestinal disturbances, such as , , and dry mouth, which typically resolve within a few days, especially at higher doses. Less frequently, effects like and have been reported, but these are rare and do not include substantial or psychomotor deficits, even during short-term use. Rare but serious adverse reactions may include paradoxical excitation, characterized by increased agitation or , though such events are infrequent and have been documented in isolated cases. Allergic reactions, such as skin rash, can also occur but are uncommon. Compared to 1,4-benzodiazepines like , tofisopam exhibits a notably lower incidence of dependence and withdrawal symptoms, with profiles resembling those of in controlled studies. No evidence of tolerance development has been observed in standard treatment durations. For long-term risks, short-term administration shows minimal cognitive effects, supporting its use without the typical impairments seen in other anxiolytics.

Contraindications and Precautions

Tofisopam is contraindicated in patients with known to the drug or other benzodiazepines, as this may lead to severe allergic reactions. It is also contraindicated in individuals with severe or depression, decompensated , or a history of syndrome. Additionally, tofisopam should not be used during the first trimester of due to potential fetal risks, and it is contraindicated during , as the drug may pass into and affect the . Caution is advised in patients with severe hepatic or renal impairment, where the drug's metabolism and elimination may be significantly compromised, increasing the risk of toxicity. Relative precautions are advised for certain patient groups to minimize risks. In patients with a history of substance abuse, tofisopam should be used cautiously despite its low potential for dependence and abuse, characteristic of 2,3-benzodiazepines which lack significant sedative or euphoric effects. Elderly patients exhibit increased sensitivity to the drug's effects, necessitating a reduced daily dose by approximately twofold to avoid excessive sedation or cognitive impairment. Co-administration with CYP3A4 substrates, such as certain antidepressants (e.g., duloxetine) or antifungals (e.g., ketoconazole), requires caution, as tofisopam inhibits CYP3A4, potentially elevating substrate levels and enhancing adverse effects; dose adjustments or monitoring of substrate concentrations are recommended for management. Similarly, concurrent use with CNS depressants like alcohol or other sedatives can potentiate respiratory depression and sedation, warranting avoidance or careful titration. In cases of overdose, management is primarily supportive, including monitoring and providing respiratory support if needed, as deaths are rare when tofisopam is taken alone without . There is no specific such as , due to tofisopam's atypical pharmacodynamic profile which differs from classical benzodiazepines; use has not been clinically tested for this agent and is reserved only for life-threatening situations.

Pharmacology

Pharmacodynamics

Tofisopam is a 2,3- derivative that acts primarily as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs), with the highest affinity for PDE-4A1 (IC₅₀ = 0.42 μM), followed by PDE-10A1 (IC₅₀ = 0.92 μM), PDE-3 (IC₅₀ = 1.98 μM), and PDE-2A3 (IC₅₀ = 2.11 μM). This inhibition elevates intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), potentially enhancing downstream signaling pathways such as that support its therapeutic actions. Unlike classical 1,4-s, tofisopam lacks affinity for the primary site on GABA_A receptors and does not impair motor skills or induce , distinguishing its pharmacological profile. Preclinical studies have shown that tofisopam does not bind directly to the or GABA recognition sites on GABA_A receptors but can enhance the binding of benzodiazepines (e.g., [³H] in and hippocampus by 13.7–22.9% at 300 mg/kg in mice) and the GABA , potentially facilitating transmission without typical effects. Tofisopam uniquely potentiates the effects of and 1,4-s like in preclinical models but does not interact similarly with sodium , , , or , indicating a specific augmentation of GABA-mediated activity. Preclinical studies further highlight tofisopam's PDE-10A blockade, which suggests potential antipsychotic-like effects beyond anxiety treatment. In a mouse model of negative symptoms of induced by , tofisopam at 50 mg/kg intraperitoneally significantly reduced immobility (p < 0.004), mimicking alleviation of avolition-like behaviors, with effects persisting up to three days post-administration. This combined partial inhibition of PDE-4, PDE-10, and PDE-2 may underlie its efficacy in such models while maintaining a favorable safety profile, avoiding emetic side effects associated with selective PDE-4 inhibitors.

Pharmacokinetics

Tofisopam exhibits favorable pharmacokinetic properties that support its use as an oral anxiolytic, characterized by rapid onset and a relatively short duration of action. Following oral administration, the drug is quickly absorbed from the gastrointestinal tract, achieving peak plasma concentrations within 1 to 2 hours. This rapid absorption profile aligns with its two-compartment open model pharmacokinetics observed in human studies. Distribution of tofisopam occurs widely throughout the body, with an apparent volume of distribution ranging from approximately 500 to 5,000 L, indicating substantial extravascular penetration and efficient crossing of the blood-brain barrier to exert central effects. Plasma protein binding is high at around 99%, primarily to albumin, which limits the free fraction available for tissue distribution but does not impede its CNS activity. No significant accumulation occurs beyond steady-state levels reached after 2 to 3 days of multiple dosing. Metabolism of tofisopam is primarily hepatic, through cytochrome P450 enzymes, notably for the (S)-enantiomer and for the (R)-enantiomer, leading to demethylation of methoxy groups on the aromatic rings. The resulting metabolites are inactive and undergo glucuronic acid conjugation, with no active metabolites contributing to the pharmacological effects. Excretion occurs mainly via the kidneys, with 60-70% of the dose eliminated as conjugated metabolites in urine over 24-48 hours, and a smaller portion in feces; the elimination half-life of unchanged tofisopam is approximately 3-6 hours. Pharmacokinetic parameters may be altered in certain conditions; for instance, hepatic impairment can lead to mild prolongation of half-life due to reduced metabolic clearance, necessitating dose adjustments. There is no significant effect of food on absorption or overall bioavailability, which is nearly complete.

Chemistry

Structure and Properties

Tofisopam is a derivative of the 2,3-benzodiazepine class, known by the IUPAC name 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine. It features a fused benzene and diazepine ring system with specific substituents that distinguish it from classical 1,4-benzodiazepines. Its chemical structure includes a 3,4-dimethoxyphenyl group attached at the 1-position, an ethyl substituent at the 5-position, a methyl group at the 4-position, and methoxy groups at the 7- and 8-positions of the benzodiazepine core. The molecular formula of tofisopam is C₂₂H₂₆N₂O₄, and its molar mass is 382.46 g/mol. Tofisopam exists as a racemic mixture of its (R)- and (S)-enantiomers, each of which can adopt two stable boat conformations due to the flexibility of the seven-membered diazepine ring. The (R)-enantiomer, known as dextofisopam, exhibits greater potency in preclinical models of anxiety and gastrointestinal disorders compared to the (S)-enantiomer or the racemate. Chiral separation of these enantiomers can be achieved through methods such as using chiral stationary phases, , or recrystallization of diastereomeric salts formed with chiral resolving agents. Physically, tofisopam appears as a white to off-white crystalline powder. It is practically insoluble in water (approximately 0.0024 mg/mL at 25°C) but shows better solubility in organic solvents, such as being slightly soluble in ethanol (95%) and freely soluble in chloroform and acetone. Its melting point ranges from 152–159°C. Under normal storage conditions (e.g., at room temperature in a dry environment), tofisopam demonstrates good stability, with no significant degradation reported in pharmaceutical formulations over typical shelf lives.

Synthesis

Tofisopam, a 2,3-benzodiazepine anxiolytic, was originally synthesized in Hungary during the late 1960s to early 1970s through a multi-step process culminating in the formation of its characteristic fused ring system. The key precursor is the 1,5-diketone 3-[2-(3,4-dimethoxybenzoyl)-4,5-dimethoxyphenyl]pentan-2-one, which undergoes reaction with hydrazine or hydrazine hydrate to form a hydrazone intermediate. This intermediate then cyclizes under acid catalysis—typically using an inorganic acid such as hydrochloric acid in a lower aliphatic alcohol solvent—to yield the benzodiazepine ring, distinguishing tofisopam from 1,4-benzodiazepines by the positioning of the nitrogen atoms at the 2,3-positions. The resulting product is isolated by treatment with an acid-binding agent like ammonium hydroxide, achieving yields of approximately 71% with a melting point of 156–157°C. The 1,5-diketone precursor itself is classically prepared via oxidation of an isochromane intermediate, such as 1-(3,4-dimethoxyphenyl)-4-ethyl-6,7-dimethoxy-3-methylisochromane, using chromium(VI) oxide in sulfuric acid at low temperatures (0–5°C) in acetone, followed by extraction with ethyl acetate. This step introduces the necessary carbonyl functionality for subsequent cyclization while maintaining the 2,3-substitution pattern inherent to the benzophenone-derived scaffold. Earlier stages involve condensation of 3-(3,4-dimethoxyphenyl)pentan-2-ol with 3,4-dimethoxybenzaldehyde in the presence of gaseous HCl in dioxane, forming the isochromane ring under reflux conditions. Due to the chirality at the 5-position, enantioselective synthesis of dextofisopam (the (R)-) typically employs chiral resolution of racemic tofisopam using (R,R)-dibenzoyl-L-tartaric acid in a toluene-chloroform mixture, followed by recrystallization of the diastereomeric salt to achieve high enantiomeric purity (>99%). Alternative approaches include asymmetric catalysis in the construction of the diketone precursor, though resolution remains the predominant method for isolating the active . Industrial production has evolved to optimize for pharmaceutical-grade purity, replacing chromium-based oxidations with chromium-free alternatives to avoid environmental concerns. For instance, lithiation of brominated intermediates with n-butyllithium at low temperatures (-78°C), followed by reaction with 3,4-dimethoxybenzoic acid derivatives and ketal hydrolysis using dilute sulfuric acid, yields the diketone in 32–50% overall efficiency. Final cyclization with hydrazine in ethanol or acetic acid, combined with purification via crystallization from ethanol or chromatography on silica gel, ensures >98% purity and batch yields of 70–93% for the benzodiazepine formation step. These processes emphasize scalable, high-yield reactions while minimizing hazardous reagents.

Development and History

Discovery and Early Research

Tofisopam, a member of the 2,3-benzodiazepine class, was first synthesized in the late 1960s by Hungarian chemists at Egis Pharmaceuticals (formerly part of the Chinoin group) as part of efforts to develop s with reduced properties compared to classical 1,4-s. The compound, initially coded as EGYT-341, was described in the original Hungarian HU 155,572, filed on August 27, 1968, which covered its and basic synthesis methods involving the cyclization of appropriate derivatives with . This work built on broader explorations of analogs aimed at achieving effects without the , muscle relaxation, or typical of earlier agents like . Early preclinical research in the and focused on animal models to evaluate tofisopam's pharmacological profile. Studies in demonstrated activity in models of anxiety, such as the punished drinking test and elevated plus-maze, where tofisopam reduced fear-related behaviors at doses of 10–50 mg/kg without inducing or significant , unlike classical benzodiazepines. For instance, in water-immersion stress models in rats, tofisopam (30–100 mg/kg orally) inhibited gastric ulceration—a marker of anxiety—dose-dependently, while showing no impairment in tests. Differentiation from classical benzodiazepines emerged through radioligand binding assays in the early 1980s, revealing tofisopam's atypical interaction with the GABA_A receptor complex. Unlike 1,4-s, tofisopam did not directly bind to the benzodiazepine recognition site but enhanced the affinity of agonists like for GABA_A receptors in forebrain membranes, increasing [³H] binding by approximately 17% at 1 μM concentrations . Multiple-dose administration (50 mg/kg orally twice daily for six days) in s also modulated [³H] binding, suggesting indirect effects on benzodiazepine receptor affinity without the typical allosteric potentiation of GABA. These findings, published in key papers such as those in Pharmacology Biochemistry and Behavior (1982) and in Neuro-Psychopharmacology & Biological Psychiatry (1982), established tofisopam's unique profile in anxiety models, highlighting its potential as a non-sedative . The HU 155,572 provided foundational protection for tofisopam and its synthesis, with subsequent international filings in the 1970s extending coverage; for example, the compound's utility was further detailed in related Hungarian patents like HU 179,018 (filed 1975), emphasizing its preclinical efficacy in animal stress paradigms. These early developments at Egis laid the groundwork for tofisopam's approval in in 1975 under the brand name Grandaxin, marking a shift toward atypical benzodiazepines.

Clinical Trials and Approval

Early clinical trials for tofisopam, conducted primarily in the 1970s, demonstrated its efficacy in with anxiety . A -controlled study involving with anxiety symptoms showed that tofisopam significantly reduced anxiety ratings compared to , with minimal impairment of cognitive function and fewer adverse effects such as . Another comparative trial confirmed tofisopam's effectiveness in alleviating anxiety and associated depression, as assessed by both physician and self-ratings, without the properties typical of classical benzodiazepines. These phase II studies, often involving doses of 100–300 mg daily, established its tolerability in anxiety , paving the way for broader evaluation. Trials for alcohol withdrawal in the early 1980s further supported tofisopam's utility, showing it reduced withdrawal symptoms like tremors and agitation with efficacy comparable to traditional benzodiazepines but less . In one study of patients with chronic , tofisopam at 300 mg daily effectively managed acute withdrawal phases, improving compliance due to its favorable side-effect profile. These findings from phase II evaluations in highlighted its potential as an alternative for short-term use in withdrawal syndromes. Tofisopam received initial approval in in January 1975 for the treatment of anxiety disorders, marking its first regulatory authorization in . It was subsequently approved in several other Eastern European countries during the late 1970s and 1980s, and expanded to additional European nations including by the . By the early , marketing authorizations had been granted in several EU member states under the brand name Grandaxin for indications. Tofisopam has not received approval from the U.S. FDA and remains unapproved in the United States and . In the 2000s, development focused on the D-enantiomer, dextofisopam, for (IBS) by Vela Pharmaceuticals. Phase II trials demonstrated that dextofisopam (200–600 mg daily) improved stool consistency and reduced frequency in patients with diarrhea-predominant IBS, with benefits observed in both men and women after 12 weeks of treatment. These studies, including a randomized, placebo-controlled evaluation, showed statistically significant symptom relief without major safety concerns, supporting its promise as a novel IBS therapy. However, further development was halted due to corporate challenges and lack of funding after Phase IIb trials, preventing advancement to Phase III. Research has explored tofisopam's potential in through its inhibition of 10A (PDE10A), with preclinical studies indicating activity against negative symptoms in animal models, positioning it as a candidate for adjunctive . More recent studies, including a 2024 double-blind, randomized, crossover trial, have confirmed tofisopam's efficacy comparable to but with fewer side effects. Additionally, case series from 2021 have reported its utility in managing post-COVID-19 neuropsychiatric symptoms, such as anxiety and catatonia, without . Post-approval surveillance has confirmed tofisopam's low abuse potential, attributed to its lack of direct agonism and minimal reinforcing effects compared to classical benzodiazepines. Long-term studies and meta-analyses of clinical data report no significant withdrawal symptoms beyond levels and rare instances of dependence, even after extended use. Regulatory guidelines in approving countries, such as those in the , limit prescriptions to a maximum of 12 weeks to mitigate any residual risks associated with prolonged therapy.

Society and Culture

Tofisopam is classified as a prescription-only in the countries where it has received regulatory approval, including several European nations such as , , the , and . In these jurisdictions, it is regulated as a prescription-only , reflecting its low potential due to the atypical 2,3-benzodiazepine that minimizes and muscle-relaxant effects. Due to its low risk of physical or , even with prolonged use, tofisopam is not scheduled as a under the 1971 or the 1961 . In the United States, tofisopam has not been approved by the (FDA) for marketing or sale. Similarly, it lacks approval from . Importing tofisopam into these countries is considered importation of an unapproved new drug, which is generally prohibited under federal regulations to ensure safety, efficacy, and quality standards are met. Efforts to develop its D-enantiomer (dextofisopam) for conditions like reached phase II trials but did not progress to approval, highlighting challenges in demonstrating sufficient clinical benefits. Tofisopam is available by prescription in various other regions, including parts of beyond the aforementioned EU countries, as well as in (such as and ). As of October 2025, it is nationally authorised in the in , , , and , with availability also reported in other European countries such as and . Its regulatory status remains unscheduled under international conventions in these areas, aligning with its profile of minimal dependence risk. Non-approval in major Western markets like the and Canada stems from regulatory requirements for comprehensive long-term safety data and comparative evidence against established anxiolytics, areas where tofisopam has not met submission thresholds despite its approval elsewhere since 1975. This contrasts with its established use in approving countries, where post-marketing surveillance has supported its safety profile without significant concerns.

Availability and Brand Names

Tofisopam is primarily available in the form of 50 mg oral tablets, with both branded and generic formulations offered by various manufacturers. Some generic versions in markets like also include 100 mg tablets. Common brand names for tofisopam include Grandaxin, which is widely used in and , as well as Emandaxin and Sériel in select regions. Generic versions are marketed simply as Tofisopam in countries such as and . The D-enantiomer, known as dextofisopam, has been researched for potential therapeutic applications but remains in development without a commercial brand name. Tofisopam is marketed in several countries, including , , , , , , , and others such as , Georgia, , , , , , and . It is not approved or commercially available in the United States, , or . Following the expiry of its original patents from the 1970s, tofisopam has seen widespread generic production, contributing to its availability in regional markets but limiting broader global distribution due to varying national approvals and regulatory requirements.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Tofisopam
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC2993883/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC10820453/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC8313453/
  5. https://www.drugs.com/international/tofisopam.html
  6. https://go.drugbank.com/drugs/DB08811
  7. https://pubmed.ncbi.nlm.nih.gov/17973974/
  8. https://www.vinmec.com/eng/blog/uses-of-tofisopam-en
  9. https://www.practo.com/medicine-info/tofisopam-2216-api
  10. https://www.mims.com/singapore/drug/info/tofisopam?mtype=generic
  11. https://www.rad-ar.or.jp/siori/english/search/result?n=38218
  12. https://synapse.patsnap.com/article/what-is-tofisopam-used-for
  13. https://drugtodayonline.com/drug-directory/drug_info/tofisopam
  14. https://www.inchem.org/documents/pims/pharm/pim686.htm
  15. https://www.medixlife.com/grandapam-instructions/
  16. https://pubmed.ncbi.nlm.nih.gov/2874535/
  17. https://pubmed.ncbi.nlm.nih.gov/32777/
  18. https://pubmed.ncbi.nlm.nih.gov/6124072/
  19. https://patents.google.com/patent/EP1124556B1/en
  20. https://pubmed.ncbi.nlm.nih.gov/8100114/
  21. https://russianmeds.com/pdf/tofisopam.pdf
  22. https://www.sciencedirect.com/science/article/abs/pii/S1385299X99000252
  23. https://www.sciencedirect.com/science/article/pii/S0031698982800623
  24. https://pubmed.ncbi.nlm.nih.gov/8100112/
  25. https://pubmed.ncbi.nlm.nih.gov/8100113/
  26. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/tofisopam
  27. https://pubmed.ncbi.nlm.nih.gov/17989974/
  28. https://www.sigmaaldrich.com/US/en/product/sigma/t8200
  29. https://pubmed.ncbi.nlm.nih.gov/29999177/
  30. https://www.researchgate.net/publication/6941888_Method_validation_and_determination_of_enantiomers_and_conformers_in_tofisopam_drug_substances_and_drug_products_by_chiral_high-performance_liquid_chromatography_and_kinetic_and_thermodynamic_study_of
  31. https://onlinelibrary.wiley.com/doi/10.1155/2019/4980792
  32. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3738807
  33. https://jpdb.nihs.go.jp/jp14e/14data/Part-I/Tofisopam.pdf
  34. https://patents.google.com/patent/US3736315A/en
  35. https://patents.google.com/patent/US20040229866A1/en
  36. https://patents.google.com/patent/WO2003050092A2/en
  37. https://patents.google.com/patent/WO2004054951A1/en
  38. https://www.researchgate.net/publication/307528691_Synthesis_of_14-diarylpyrrolotriazepine_derivatives_by_two_diverse_strategies
  39. https://pubmed.ncbi.nlm.nih.gov/6136319/
  40. https://www.sciencedirect.com/science/article/abs/pii/S0031698982800817
  41. https://www.sciencedirect.com/science/article/pii/0091305782900946
  42. https://patents.google.com/patent/CN101823945B/en
  43. https://synapse.patsnap.com/blog/an-in-depth-analysis-of-tofisopams-randd-progress
  44. https://psychiatryonline.org/doi/10.1176/ajp.136.2.196
  45. https://www.worldwidejournals.com/indian-journal-of-applied-research-%28IJAR%29/recent_issues_pdf/2014/October/October_2014_1492783009__129.pdf
  46. https://go.gale.com/ps/i.do?id=GALE%257CA692413842&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=23275707&p=AONE&sw=w
  47. https://www.ema.europa.eu/en/documents/psusa/tofisopam-list-nationally-authorised-medicinal-products-psusa-00002982-202501_en.pdf
  48. https://journals.lww.com/ajg/fulltext/2005/09001/dextofisopam_improves_bowel_function_in_men_and.941.aspx
  49. https://www.biospace.com/pharmos-corporation-issues-business-update-on-dextofisopam-trial-and-financing
  50. https://journals.sagepub.com/doi/10.1177/0253717621994285
  51. https://www.mdpi.com/1424-8247/17/1/140
  52. https://assets.publishing.service.gov.uk/media/5ea95a1cd3bf7f6523c81c01/ACMD_report_-_a_review_of_the_evidence_of_use_and_harms_of_novel_benzodiazepines.pdf
  53. https://pdfs.semanticscholar.org/4857/6f3aea67cef37a8c33dbb3483117944b46b4.pdf
  54. https://www.vinmec.com/eng/blog/what-does-grandaxin-50mg-do-en
  55. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/frequently-asked-questions-about-drugs
  56. https://dati.zva.gov.lv/zalu-registrs/?iss=1&q=Tofisopamum&lang=en
  57. https://www.1mg.com/generics/tofisopam-212600
  58. https://www.pharmacompass.com/active-pharmaceutical-ingredients/tofisopam
Add your contribution
Related Hubs
User Avatar
No comments yet.