Comparative outcomes achieved with a dosage of chlormezazone that inhibited the contralateral extensor muscles by more than 80% [1].

Absorption, Distribution and Excretion
RAPIDLY ABSORBED FROM GI TRACT...EFFECT WITHIN 15 TO 30 MIN...DURATION OF ACTION OF 4 TO 6 HR...FREE DRUG & /4-CHLOROHIPPURIC ACID/ EXCRETED IN URINE /HUMAN, ORAL/...PRESENT IN HIGH CONCN IN KIDNEY, LIVER, MUSCLE, HEART, & BODY FAT, & IN LESSER CONCN IN LUNG & PLASMA /RATS, ORAL/.
AFTER ORAL ADMIN OF (14)C-CHLORMEZANONE, ABOUT 74% OF DOSE WAS EXCRETED INTO URINE OF RATS WITHIN 24 HR & 21% INTO URINE OF MICE WITHIN 2 HR. BILIARY EXCRETION OF RADIOACTIVITY WAS ABOUT 10% OF DOSE IN RATS.

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Metabolism / Metabolites
CHLORMEZANONE...IS EXCRETED UNCHANGED IN HUMAN URINE & DOG BILE. FORMATION OF 4-CHLOROHIPPURIC ACID, MAJOR URINARY METABOLITE IN MAN, INVOLVES NON-ENZYMIC HYDROLYSIS, FOLLOWED BY OXIDATION & CONJUGATION OF 4-CHLOROBENZALDEHYDE PRODUCT OF HYDROLYSIS.
(14)C-CHLORMEZANONE, METABOLITES IN URINE OF RATS & MICE WERE P-CHLOROBENZOIC ACID, P-CHLOROHIPPURIC ACID, N-METHYL-P-CHLOROBENZAMIDE, 2-[N-METHYL-N-(P-CHLOROBENZOYL)]CARBAMOYLETHYLSULFONIC ACID, 3-SULFOPROPIONIC ACID & GLUCURONIDE OF P-CHLOROBENZOIC ACID.

Toxicity Summary
Chlormezanone binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

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Interactions
CHLORMEZANONE MAY LOWER TOLERANCE OF PATIENTS TO ALCOHOL...POSSIBLE ADDITIVE EFFECTS /WITH CHLORMEZANONE &/ CNS DEPRESSANTS SUCH AS ALCOHOL, PHENOTHIAZINES, BARBITURATES, NARCOTICS, OTHER PSYCHOTHERAPEUTIC AGENTS, & MONOAMINE OXIDASE INHIBITORS.

[1]. EFFECTS OF NEW s-TRIAZOLOBENZODIAZEPINE (D-4OTA) AND OTHER CENTRAL MUSCLE RELAXANTS ON SPINAL AND SUPRASPINAL REFLEXES IN CATS. Japan. J. Pharmacol, 23, 83-96 (1973).

Chlormezanone is a 1,3-thiazine that is 1,3-thiazinan-4-one S,S-dioxide in which a hydrogen at position 2 is substituted by a 4-chlorophenyl group and the hydrogen attached to the nitrogen is substituted by methyl. A non-benzodiazepine muscle relaxant, it was used in the management of anxiety and in the treatment of muscle spasms until being discontinued worldwide by its manufacturer in 1996, due to rare but serious cutaneous reactions. It has a role as an anxiolytic drug, a muscle relaxant and an antipsychotic agent. It is a 1,3-thiazine, a lactam, a sulfone and a member of monochlorobenzenes.
A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm.
Chlormezanone is only found in individuals that have used or taken this drug. It is a non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm. [PubChem]Chlormezanone binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm.

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Drug Indication
Used in the management of anxiety and in the treatment of muscle spasm.

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Mechanism of Action
Chlormezanone binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
NEURONAL CONDUCTION, NEUROMUSCULAR TRANSMISSION, & MUSCLE EXCITABILITY ARE NOT DEPRESSED EXCEPT AFTER NEARLY LETHAL DOSES. PROMINENT EFFECT...IS TO DEPRESS SPINAL POLYSYNAPTIC REFLEXES PREFERENTIALLY OVER MONOSYNAPTIC REFLEXES. /CENTRALLY ACTING MUSCLE RELAXANTS/
IN ABSENCE OF DEFINITIVE STUDIES IT APPEARS REASONABLE TO ASCRIBE BENEFICIAL EFFECTS...TO THEIR SEDATIVE PROPERTIES. /CENTRALLY ACTING MUSCLE RELAXANTS/

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Therapeutic Uses
Anti-Anxiety Agents; Muscle Relaxants, Central
...ADMIN IV HAVE ESTABLISHED VALUE IN TREATING ACUTE MUSCLE SPASMS ASSOC WITH TRAUMA & INFLAMMATION. ...ALSO BENEFICIAL IN PRODUCING MUSCLE RELAXATION FOR CERTAIN ORTHOPEDIC MANIPULATIONS. ...MAY TEMPORARILY ABATE SOME OF SYMPTOMS OF CEREBRAL PALSY... /CENTRALLY ACTING MUSCLE RELAXANTS/
MANY AGENTS WITH MUSCLE RELAXANT PROPERTIES PRODUCE NOTABLE SEDATION IN ORDINARY ORAL DOSES. SUCH AGENTS ENJOY PARTICULARLY WIDE USE IN TREATMENT OF MUSCLE TENSION & PAINS ASSOC WITH ANXIETY STATES & PSYCHOSOMATIC DISORDERS. /CENTRALLY ACTING MUSCLE RELAXANTS/
MUSCLE RELAXANTS CAUSE SKELETAL MUSCULAR RELAXATION, WITHOUT LOSS OF CONSCIOUSNESS, AS RESULT OF SELECTIVE ACTION UPON CNS. ... ALL TYPES OF EXPTL HYPERTONIA & HYPERREFLEXIA...PRODUCED BY SPINAL OR SUPRASPINAL LESIONS, ARE DIMINISHED... ALSO...PROTECTION AGAINST...CONVULSIVE AGENTS... /CENTRALLY ACTING MUSCLE RELAXANTS/
...AS EFFECTIVE AS CHLORDIAZEPOXIDE IN TREATING MILD ANXIETY. MUSCULOSKELETAL DISORDERS IN WHICH ANXIETY & TENSION INTENSIFY SYMPTOMS MAY RESPOND TO ITS SEDATIVE EFFECT...DOES NOT APPEAR TO HAVE ANY SPECIFIC EFFECT ON SPASTICITY OR RIGIDITY ASSOC WITH ORG NEUROLOGIC DISORDERS.

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Drug Warnings
SOMETIMES METABOLITE DISCOLORS URINE.
UNTOWARD EFFECTS ARE GENERALLY MILD & OCCUR RELATIVELY INFREQUENTLY BUT, IN 2 CONTROLLED STUDIES, REACTIONS WERE MORE COMMON...THAN WITH CHLORDIAZEPOXIDE.
...PRODUCE SOME SEDATION, @ LEAST @ HIGHEST DOSES EMPLOYED CLINICALLY. /CENTRALLY ACTING MUSCLE RELAXANTS/

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Pharmacodynamics
Chlormezanone is a non-benzodiazepine muscle relaxant. It was discontinued worldwide in 1996 by its manufacturer due to confirmed serious and rare cutaneous reactions (toxic epidermal necrolysis).

C11H12CLNO3S

273.74

273.022

80-77-3

2717

White to off-white solid powder

1.4±0.1 g/cm3

534.5±50.0 °C at 760 mmHg

114ºC

277.1±30.1 °C

0.0±1.4 mmHg at 25°C

1.580

0.86

0

3

1

17

395

0

WEQAYVWKMWHEJO-UHFFFAOYSA-N

InChI=1S/C11H12ClNO3S/c1-13-10(14)6-7-17(15,16)11(13)8-2-4-9(12)5-3-8/h2-5,11H,6-7H2,1H3

2-(4-chlorophenyl)-3-methyl-1,1-dioxo-1,3-thiazinan-4-one

Trancopal; Chlormethazanone; Chlormezanone

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 : ≥ 100 mg/mL (~365.31 mM)
H2O : ~0.67 mg/mL (~2.45 mM)

Solubility in Formulation 1: ≥ 3.25 mg/mL (11.87 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 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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.

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Solubility in Formulation 2: ≥ 3.25 mg/mL (11.87 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 32.5 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.

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Solubility in Formulation 3: ≥ 3.25 mg/mL (11.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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