Comparison of neurotropic effects of L-glutamic acid and its new derivative β-phenylglutamic acid hydrochloride (RGPU-135, glutarone).
In contrast to L-glutamic acid (200 mg/kg), β-phenylglutamic acid hydrochloride (26 mg/kg) produces no anticonvulsant effects during generalized convulsions induced by "maximum electric shock". However, β-phenylglutamic acid hydrochloride was more potent than L-glutamic acid in increasing survival rate, promoting recovery of spontaneous motor activity, and maintainance locomotor and exploratory activity in the open field test and cognitive functions in conditioned passive avoidance test, i.e. exhibited neuroprotective activity. This substance did not change the threshold of pain induced by electric stimulation of paws (up to vocalization) and thermal tail stimulation (tail-flick), whereas L-glutamic acid decreased this parameter. β-Phenylglutamic acid suppressed aggression in the test for provoked unmotivated aggression, while L-glutamic acid enhanced it. Due to these neurotropic effects, β-phenylglutamic acid hydrochloride can be used as the basis for the development of drugs with antidepressant, anxiolytic, and neuroprotective actions.
Volgograd State Medical University, Volgograd, Russia.
I N
IN
Tyurenkov
V V
VV
Bagmetova
Yu V
YV
Chernysheva
O V
OV
Merkushenkova
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004558:Electric Stimulation / Q000009:adverse effects*; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control; D015996:Survival Rate
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D000928:Antidepressive Agents; D018696:Neuroprotective Agents; C581791:RGPU-135; D018698:Glutamic Acid