Monograph: |
TOFISOPAM
DESCRIPTION
TOFISOPAM (MARKETED UNDER BRAND NAMES EMANDAXIN AND GRANDAXIN) IS A 2,3-BENZODIAZEPINE DRUG WHICH IS A BENZODIAZEPINE DERIVATIVE. IN CONTRAST TO CLASSICAL 1,4-BENZODIAZEPINES, THE COMPOUND DOES NOT BIND TO THE BENZODIAZEPINE BINDING SITE OF THE GAMMA-AMINOBUTYRIC ACID RECEPTOR AND ITS PSYCHOPHARMACOLOGICAL PROFILE DIFFERS FROM SUCH COMPOUNDS. ALTHOUGH TOFISOPAM IS NOT APPROVED FOR SALE IN NORTH AMERICA, IT IS APPROVED FOR USE IN VARIOUS COUNTRIES WORLDWIDE, INCLUDING PARTS OF EUROPE. THE D-ENANTIOMER (DEXTOFISOPAM ) IS CURRENTLY IN PHASE II TRIALS IN THE U.S. FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME.
PHARMACOLOGY
INDICATION
FOR THE TREATMENT OF ANXIETY AND ALCOHOL WITHDRAWAL.
PHARMACODYNAMICS
LIKE OTHER BENZODIAZEPINES, TOFISOPAM POSSESSES ANXIOLYTIC PROPERTIES BUT UNLIKE OTHER BENZODIAZEPINES IT DOES NOT HAVE ANTICONVULSANT, SEDATIVE, SKELETAL MUSCLE RELAXANT, MOTOR SKILL-IMPAIRING OR AMNESTIC PROPERTIES. IT ENHANCES THE ANTICONVULSANT ACTIVITY OF 1,4-BENZODIAZEPINES LIKE DIAZEPAM BUT NOT SODIUM VALPROATE, CARBAMAZEPINE, PHENOBARBITAL, OR PHENYTOIN.
MECHANISM OF ACTION
TOFISOPAM DOES NOT BIND TO THE BENZODIAZEPINE BINDING SITE OF THE GAMMA-AMINOBUTYRIC ACID RECEPTOR. ONE STUDY (RUNDFELDT C. ET AL.) HAS SHOWN THAT TOFISOPAM ACTS AS AN ISOENZYME-SELECTIVE INHIBITOR OF PHOSPHODIESTERASES (PDES) WITH HIGHEST AFFINITY TO PDE-4A1 (0.42 ?M) FOLLOWED BY PDE-10A1 (0.92 ?M), PDE-3 (1.98 ?M) AND PDE-2A3 (2.11 ?M).
TOXICITY
THE ONSET OF IMPAIRMENT OF CONSCIOUSNESS IS RELATIVELY RAPID IN BENZODIAZEPINE POISONING. ONSET IS MORE RAPID FOLLOWING LARGER DOSES AND WITH AGENTS OF SHORTER DURATION OF ACTION. THE MOST COMMON AND INITIAL SYMPTOM IS SOMNOLENCE. THIS MAY PROGRESS TO COMA (GRADE I OR GRADE II) FOLLOWING VERY LARGE INGESTIONS. ORAL, RAT LD50 IS 825 MG/KG.
DRUG INTERACTION
BRIMONIDINE BRIMONIDINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
DOXYLAMINE DOXYLAMINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
DRONABINOL DRONABINOL MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
DROPERIDOL DROPERIDOL MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
HYDROXYZINE HYDROXYZINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
METHOTRIMEPRAZINE METHOTRIMEPRAZINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
MINOCYCLINE MINOCYCLINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
MIRTAZAPINE MIRTAZAPINE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
NABILONE NABILONE MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
PERAMPANEL PERAMPANEL MAY INCREASE THE CENTRAL NERVOUS SYSTEM DEPRESSANT (CNS DEPRESSANT) ACTIVITIES OF TOFISOPAM.
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