Therapeutic Area(s): Anxiety
Phase of Development: Preclinical
TGSC01AA is a series of flavonoid compounds which have been shown
to have strong anxiolytic properties.
Although benzodiazepines (BDZs) are the safest psychotropic drugs
available today and hence widely prescribed as anxiolytics, their
sedative, myorelaxant and amnesic actions are often considered
unwanted side effects. Other drawbacks of these drugs include
recorded instances of ataxia, ethanol and barbiturate increased
effects, as well as their potential for drug abuse and tolerance.
Most BDZs are also associated with anterograde amnesia. Pretraining
administration of BDZs at subataxic doses impairs retention tests
For 40 years scientists have been searching for benzodiazepine-like
anxiolytics that lack amnestic, muscle relaxant, anti-convulsant,
and sedative properties. This series of compounds may be the answer
to that search.
QASAR studies show that TGSC01AA fits into the benzodiazepine
receptor site but in a different way than the benzodiazepines.
TGSC01AA has strong anxiolytic activity (up to 30x that of diazepam)
without sedative, muscle relaxant, anticonvulsant, and amnestic
TGSC01AA binds strongly to the benzodiazepine receptor, displacing
3H-FNZ. TGSC01AA enhances GABA stimulated chloride influx. In
the plus maze test and the punished drinking test TGSC01AA is
more active than diazepam predicting strong anxiolytic activity.
TGSC01AA has no hypnotic effect. For the lead compound, the ratio
between the dose that relieves anxiety and the dose that is hypnotic
is 300. For diazepam the ratio is only 3. There is no effect of
TGSC01AA on spontaneous locomotor activity in mice. There is no
effect on pentylenetetrazol induced seizures. Similarly there
are no muscle relaxant or amnestic effects.
In rat toxicity testing, no areas of concern were found up to
100 mg/kg. TGSCO1AA has low bioavailabitlity (<20%), rapid
clearance, and hepatic first pass metabolism.
No clinical trials have been performed.
Developmental and marketing partnerships are available.