Thiocolchicoside acts as a competitive antagonist at the GABAA receptor complex, enhancing the inhibitory effects of GABA in the central nervous system. This mechanism contributes to its muscle relaxant properties by reducing neuronal excitability and muscle tone. It also possesses anti-inflammatory effects by modulating the release of pro-inflammatory cytokines and inhibiting the activation of NF-κB. Additionally, thiocolchicoside has been shown to inhibit the activity of various enzymes involved in inflammation and tissue damage.

The amplitude of eIPSCs is lowered by thiocolchicoside (0.001, 0.1, 1, 10, 100 μM) in a concentration-dependent manner; this impact is substantial at 0.1 μM and reaches its maximum at 10 μM [1].
In vitro, thiocolchicoside demonstrates significant anti-inflammatory activity by reducing the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in stimulated immune cells. It also exhibits antioxidant properties by scavenging free radicals and reducing oxidative stress in cultured cells. The compound has been shown to inhibit the activation of NF-κB and the expression of COX-2 and iNOS in inflammatory cells. Its muscle relaxant activity is mediated through its action on GABAA receptors.

In vivo, thiocolchicoside exhibits muscle relaxant, anti-inflammatory, and analgesic effects in animal models. In models of muscle spasm, the compound reduces muscle tone and rigidity. In models of acute and chronic inflammation, thiocolchicoside reduces edema and pain. The compound has been shown to be effective in reducing pain and improving mobility in various musculoskeletal conditions. Its effects are mediated through both central (GABAA receptor) and peripheral (anti-inflammatory) mechanisms.

Cell-free receptor binding assays for thiocolchicoside involve assessing its affinity for the GABAA receptor complex. Radioligand binding assays using [³H]-muscimol or [³H]-flunitrazepam are used to measure the compound's ability to displace these ligands from the GABAA receptor. The compound's effects on GABA-mediated chloride influx can be measured using patch-clamp electrophysiology. Additionally, its anti-inflammatory effects can be assessed by measuring its ability to inhibit cytokine production or NF-κB activation in cell-free systems.

In vitro cellular assays for thiocolchicoside use various cell types, including neuronal cells for studying GABAA receptor modulation and immune cells for studying anti-inflammatory effects. For GABA receptor studies, neuronal cell lines are treated with thiocolchicoside, and changes in intracellular chloride levels are measured using fluorescent indicators. For anti-inflammatory studies, macrophages are stimulated with LPS, and cytokine production is measured by ELISA. The compound's effects on cell viability and proliferation are assessed using standard cell viability assays.

In vivo animal studies for thiocolchicoside typically use rodent models of muscle spasm, inflammation, and pain. In the model of muscle spasm, the compound's effects on muscle tone are assessed using electromyography. In the carrageenan-induced paw edema model, the compound's anti-inflammatory effects are evaluated by measuring paw volume. In analgesic studies, the hot plate test and formalin test are used. The compound is administered via oral or intraperitoneal routes.

Absorption, Distribution and Excretion
Oral bioavailability is approximately 25%. Following intramuscular injection, peak plasma concentration (Cmax) of colchicine is reached within 30 minutes, reaching 113 ng/mL after a 4 mg dose and 175 ng/mL after an 8 mg dose. The corresponding AUC values are 283 ng·h/mL and 417 ng·h/mL, respectively. The concentration of the pharmacologically active metabolite SL18.0740 is lower, reaching Cmax of 11.7 ng/mL at 5 hours post-administration, with an AUC of 83 ng·h/mL. After oral administration, colchicine was not detected in plasma. Only two metabolites were observed: the pharmacologically active metabolite SL18.0740 and the inactive metabolite SL59.0955. Peak plasma concentrations of both metabolites occurred 1 hour after colchicine administration. Following a single oral dose of 8 mg colchicine, the Cmax and AUC of SL18.0740 were approximately 60 ng/mL and 130 ng·h/mL, respectively. These values were much lower for SL59.0955: Cmax was approximately 13 ng/mL, and AUC ranged from 15.5 ng·h/mL (to 3 hours) to 39.7 ng·h/mL (to 24 hours). Colchicine is not excreted unchanged but exists as one of three metabolites, approximately 79% of which are found in feces and 20% in urine. 3-Desmethylcolchicine (M2) and 3-O-glucuronide-desmethylcolchicine (M1) are found in both urine and feces, while didesmethylcolchicine is found only in feces. The apparent volume of distribution after an intramuscular injection of 8 mg colchicine is estimated to be approximately 42.7 L.
Primarily cleared via extrarenal route (accounting for 75% of systemic clearance).

---

Metabolisms/Metabolites
Thiocolchicine is rapidly absorbed after oral administration and metabolized into three major metabolites. It is first metabolized in the intestine to 3-demethylcolchicine (an inactive metabolite). Further metabolism occurs in circulation, either through conjugation with 3-O-glucuronic acid-demethylcolchicine (the active metabolite) or demethylation to didemethylcolchicine (an inactive metabolite).

---

Biological half-life
Approximately 7.7 hours.
Thiocolchicoside has a molecular formula of C₂₇H₃₃NO₁₀S and a molecular weight of 563.62. It is a glucoside of colchicine with improved safety and tolerability compared to the parent compound. Thiocolchicoside is used as a muscle relaxant and anti-inflammatory agent in the treatment of painful muscle spasms and musculoskeletal conditions. It is administered orally or topically. Its pharmacokinetic profile includes good oral absorption, with metabolism primarily by the liver and excretion in urine and feces.

Protein Binding
The binding of 3H-colchicine and its derivative 3H-thiocolchicine to human serum, purified human protein, and erythrocytes was studied using balanced dialysis and centrifugation. The binding rates of colchicine and thiocolchicine to albumin in human serum were 38.9±4.7% and 12.8±5.3%, respectively.

[1]. The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system. Neuropharmacology. 2006 Sep;51(4):805-15.

N-[(7S)-1,2-dimethoxy-10-(methylthio)-9-oxo-3-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-2-oxacyclohexyl]oxy]-6,7-dihydro-5H-benzo[a]hepten-7-yl]acetamide is a glycoside. Thiocolchicine is a semi-synthetic derivative of colchicine, a natural anti-inflammatory glycoside extracted from the seeds of the mallow (Superba gloriosa). It has muscle relaxant, anti-inflammatory, and analgesic effects. It has a strong spasmodic effect and should not be given to patients prone to epilepsy.

---

Drug Indications
Thiocolchicine is a skeletal muscle relaxant used to treat orthopedic, traumatic, and rheumatic conditions. It can be used as an adjunct therapy for painful muscle contractures and is also indicated for acute spinal disorders in adults and adolescents aged 16 years and older. Recent studies have explored its effects on muscle tension, stiffness, contractures, and soreness experienced by athletes during athletic competition.

---

Mechanism of Action
Thiocolchicine is a synthetic sulfur derivative of colchicine, a naturally occurring glycoside found in the autumn crocus (Colchicum autumnale) plant. Thiocolchicine exhibits a selective and potent affinity for γ-aminobutyric acid A (GABA-A) receptors, relieving muscle contractures by activating the GABA inhibitory pathway, thus acting as a potent muscle relaxant. γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the human cerebral cortex. GABAergic neurons are involved in muscle relaxation, anti-anxiety therapy, sedation, and anesthesia. GABA can also regulate heart rate and blood pressure. Furthermore, GABA also has an affinity for inhibitory glycine receptors (i.e., possessing both glycoreceptor mimicry and GABA receptor mimicry activity), thus also acting as a muscle relaxant. Glycine is an inhibitory neurotransmitter that acts as an allosteric regulator of NMDA (N-methyl-D-aspartate) receptors. It is involved in the transmission of motor and sensory information, thereby modulating motor, visual, and auditory functions. It is an inhibitory neurotransmitter in the spinal cord and an allosteric regulator of NMDA receptors. One study showed that colchicine inhibits the function of recombinant human nicotinic-sensitive glycine receptors composed of the α1 subunit, with a lower inhibitory potency (IC50) than that against recombinant GABA(A) receptors. The drug also inhibits the function of human nicotinic acetylcholine receptors composed of the α4 and β2 subunits, but this inhibition is partial and only significant at high concentrations. Colchicine has no effect on the function of 5-HT(3A) serotonin receptors.

---

Pharmacodynamics
Colchicine is a muscle relaxant whose mechanism of action is through selective binding to GABA-A receptors. It inhibits muscle contraction by activating the GABA inhibitory motor pathway. This drug is a competitive GABA receptor antagonist, with an inhibitory potency against glycine receptors similar to that against nicotinic acetylcholine receptors. It has a strong convulsive effect and should not be used in patients at risk of seizures. It is used in combination with granfenicol and meprobamate for sedation in patients undergoing hysterosalpingography. Colchicine can be used to treat painful muscle spasms, effective for central contractures as well as reflex, rheumatic, and traumatic contractures. It can also relieve spastic sequelae of hemiplegia, Parkinson's disease, and iatrogenic Parkinson's disease symptoms (especially neurogenic apraxia). Other conditions that may benefit from this drug include acute and chronic low back pain and sciatica, cervicobrachial neuralgia, persistent torticollis, post-traumatic pain, and postoperative pain.
Thiocolchicoside is a semi-synthetic derivative of colchicine that is used as a muscle relaxant with anti-inflammatory and analgesic properties. It is used in the treatment of painful muscle spasms and musculoskeletal conditions. The compound has a more favorable safety profile compared to colchicine, with reduced toxicity and fewer gastrointestinal side effects. Thiocolchicoside is for research use only and not for human therapeutic use in many countries. It is available as a pharmaceutical product in certain regions for the treatment of muscle spasms.

C27H33NO10S

563.618

563.182

602-41-5

9915886

Light yellow to yellow solid powder

1.5±0.1 g/cm3

929.6±65.0 °C at 760 mmHg

190-198ºC

516.0±34.3 °C

0.0±0.3 mmHg at 25°C

1.657

-1.23

5

11

7

39

1010

6

CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)SC)OC)OC)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O

LEQAKWQJCITZNK-AXHKHJLKSA-N

InChI=1S/C27H33NO10S/c1-12(30)28-16-7-5-13-9-18(37-27-24(34)23(33)22(32)19(11-29)38-27)25(35-2)26(36-3)21(13)14-6-8-20(39-4)17(31)10-15(14)16/h6,8-10,16,19,22-24,27,29,32-34H,5,7,11H2,1-4H3,(H,28,30)/t16-,19+,22+,23-,24+,27+/m0/s1

N-[(7S)-1,2-dimethoxy-10-methylsulfanyl-9-oxo-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide

Coltramyl; R. 271; Thiocolchicoside

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~443.56 mM)
H2O : ~50 mg/mL (~88.71 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

 (Please use freshly prepared in vivo formulations for optimal results.)