Thiocolchicoside

Neuropharmacology . 2006 Sep;51(4):805-815.

The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system[Pubmed: 16806306]

Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties, and it has been shown to interact with gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and strychnine-sensitive glycine receptors in the rat central nervous system. In contrast to a proposed agonistic action at these two types of inhibitory receptors, pharmacological evidence has shown that, under certain conditions, TCC manifests convulsant activity in animals and humans. We now show that the phasic and tonic GABAAR-mediated currents recorded from Purkinje cells and granule neurons, respectively, in parasagittal cerebellar slices from adult male rats were inhibited by TCC in a concentration-dependent manner. The median inhibitory concentrations of TCC for these effects were approximately 0.15 and approximately 0.9 microM, respectively. TCC did not potentiate GABABR-mediated currents in hippocampal slices, suggesting that its muscle relaxant action is not mediated by GABABRs. Intraperitoneal injection of TCC in rats either alone or in combination with negative modulators of GABAergic transmission revealed convulsant and proconvulsant actions of this drug. Our data, consistent with clinical observations of the epileptogenic effect of this compound, suggest that TCC is a potent competitive antagonist of GABAAR function.

Cancer Prev Res (Phila) . 2010 Nov;3(11):1462-1472.

Thiocolchicoside exhibits anticancer effects through downregulation of NF-κB pathway and its regulated gene products linked to inflammation and cancer[Pubmed: 20978115]

The discovery of new uses for older, clinically approved drugs is one way to expedite drug development for cancer. Thiocolchicoside, a semisynthetic colchicoside from the plant Gloriosa superba, is a muscle relaxant and used to treat rheumatologic and orthopedic disorders because of its analgesic and anti-inflammatory mechanisms. Given that activation of the transcription factor NF-κB plays a major role in inflammation and tumorigenesis, we postulated that Thiocolchicoside would inhibit NF-κB and exhibit anticancer effects through the modulation of NF-κB-regulated proteins. We show that Thiocolchicoside inhibited proliferation of leukemia, myeloma, squamous cell carcinoma, breast, colon, and kidney cancer cells. Formation of tumor colonies was also suppressed by Thiocolchicoside. The colchicoside induced apoptosis, as indicated by caspase-3 and poly(ADP-ribose) polymerase cleavage, and suppressed the expression of cell survival [e.g., Bcl-2, X-linked inhibitor of apoptosis (XIAP), MCL-1, bcl-xL, cIAP-1, cIAP-2, and cFLIP] proteins. Cell proliferation biomarkers such as c-MYC and phosphorylation of phosphoinositide 3-kinase and glycogen synthase kinase 3β were also blocked by Thiocolchicoside. Because most cell survival and proliferation gene products are regulated by NF-κB, we studied the effect of Thiocolchicoside on this transcription factor and found that Thiocolchicoside inhibited NF-κB activation, degradation of inhibitory κBα (IκBα), IκBα ubiquitination, and phosphorylation, abolished the activation of IκBα kinase, and suppressed p65 nuclear translocation. This effect of Thiocolchicoside on the NF-κB pathway led to inhibition of NF-κB reporter activity and cyclooxygenase-2 promoter activity. Our results indicate that Thiocolchicoside exhibits anticancer activity through inhibition of NF-κB and NF-κB-regulated gene products, which provides novel insight into a half-century old drug.

Asian Pac J Allergy Immunol . 2021 Jan 2.

Immediate allergic reaction to thiocolchicoside confirmed by skin testing and basophil activation test: A case report and literature review[Pubmed: 33386791]

Background: Thiocolchicoside is a muscle relaxant, anti-inflammatory, and analgesic. Administered orally, intramuscularly, or topically, this drug is used in the symptomatic treatment of muscular spasms and rheumatologic disorders. Despite its extensive use, Thiocolchicoside is a very rare sensitizer. Objective: To evaluate IgE-mediated reaction to Thiocolchicoside by basophil activation test. Methods: Allergological work-up with skin prick tests, intradermal tests and basophil activation test with Thiocolchicoside. Results: We report the first case of immediate reaction to Thiocolchicoside confirmed by basophil activation test in addition to positive skin tests. Conclusions: BAT can be considered a complementary diagnostic tool to demonstrate an IgE-mediated reaction also for muscle relaxant drugs.

Eur Rev Med Pharmacol Sci . 2008 Jul-Aug;12(4):229-235.

Efficacy and safety of eperisone in patients with low back pain: a double blind randomized study[Pubmed: 18727454 ]

Eperisone hydrochloride (4'-ethyl-2-methyl-3-piperidinopropiophenone hydrochloride) is an antispastic agent used for treatment of diseases characterized by muscle stiffness and pain. The aim of this research was to investigate the efficacy of eperisone in patients with acute low back pain and spasticity of spinal muscles. The study design was a randomized, double-blind (double-dummy) study in 160 patients with low back pain and no Rx finding of major spinal diseases, randomly assigned to a treatment with oral eperisone 100 mg three times daily (t.i.d.) or Thiocolchicoside 8 mg twice daily (b.i.d.) for 12 consecutive days. Analgesic activity was evaluated by scoring "spontaneous pain" (VAS) and pain on movement and pression (4-digit scale), while muscle relaxant activity of the medication was evaluated by means of the "hand-to-floor" distance and the Lasegue's manoeuvre. All the measures were done at the inclusion day and after 3, 7 and 12 days of treatment. The two medications had comparable analgesic and muscle relaxant efficacy. Sponta-neous pain and pain on movement/pressure were significantly reduced by both treatments. Moreover, both eperisone- and Thiocolchicoside-treated patients showed a clinically evident muscle relaxation as proved by a progressive reduction in the "hand-to-floor" distance and increase in the articular excursion (Lasegue's manoeuvre). Only 5% of eperisone-treated patients showed minor gastrointestinal side effects, while the incidence of side effects in the Thiocolchicoside group was 21.25%. Moreover, in the Thiocolchicoside-treated patients also diarrhoea was present, which reached a moderate intensity in some cases. In conclusions, eperisone represents a valuable and safer alternative to other muscle relaxant agents for treatment of low back pain.

Br J Pharmacol . 2012 Apr;165(7):2127-2139.

Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells through inhibition of inflammatory pathways: a new use for an old drug[Pubmed: 21955206]

Background and purpose: Most patients with cancer die not because of the tumour in the primary site, but because it has spread to other sites. Common tumours, such as breast, multiple myeloma, and prostate tumours, frequently metastasize to the bone. To search for an inhibitor of cancer-induced bone loss, we investigated the effect of Thiocolchicoside, a semi-synthetic colchicoside derived from the plant Gloriosa superba and clinically used as a muscle relaxant, on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL) and tumour cells. Experimental approach: We used RAW 264.7 (murine macrophage) cells, a well-established system for osteoclastogenesis, and evaluated the effect of Thiocolchicoside on RANKL-induced NF-κB signalling and osteoclastogenesis as well as on osteoclastogenesis induced by tumour cells. Key results: Thiocolchicoside suppressed osteoclastogenesis induced by RANKL, and by breast cancer and multiple myeloma cells. Inhibition of the NF-κB pathway was responsible for this effect since the colchicoside inhibited RANKL-induced NF-κB activation, activation of IκB kinase (IKK) and suppressed inhibitor of NF-κBα (IκBα) phosphorylation and degradation, an inhibitor of NF-κB. Furthermore, an inhibitor of the IκBα kinase γ or NF-κB essential modulator, the regulatory component of the IKK complex, demonstrated that the NF-κB signalling pathway is mandatory for osteoclastogenesis induced by RANKL. Conclusions and implications: Together, these data suggest that Thiocolchicoside significantly suppressed osteoclastogenesis induced by RANKL and tumour cells via the NF-κB signalling pathway. Thus, Thiocolchicoside, a drug that has been used for almost half a century to treat muscle pain, may also be considered as a new treatment for bone loss.