Activation of brain function by S-135, a benzodiazepine receptor inverse agonist.
1. S-135, 2-(5-methylthien-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinoline-3- one, bind binds to benzodiazepine receptors with a high affinity and shows pharmacological actions opposite to those of conventional benzodiazepine drugs. 2. S-135 induced no convulsion in mice by itself, but selectively potentiated the effect of subconvulsive dose of pentylenetetrazole. 3. S-135 potentiated rat crossed extensor reflex and Ro 15-1788 completely antagonized this potentiation. 4. S-135 antagonized pentobarbital-induced anesthesia, tetrabenazine-induced ptosis and reserpine-induced hypoactivity and shortened immobilization time in the despair test in mice, indicating that this compound possesses antidepressive properties. 5. S-135 antagonized amnesia in mice and rats in passive avoidance tasks. 6. Glucose utilization in brain areas relating to memory and arousal functions was enhanced following S-135 treatment. 7. These results indicate that S-135 can be a useful drug for activating depressed brain function.
Matsushita
A
A
Division of Pharmacology, Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kawasaki
K
K
Matsubara
K
K
Eigyo
M
M
Shindo
H
H
Takada
S
S
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003863:Depression; D004195:Disease Models, Animal; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012640:Seizures / Q000503:physiopathology; D013574:Synaptosomes / Q000378:metabolism
D000928:Antidepressive Agents; D011720:Pyrazoles; D015363:Quinolones; D011963:Receptors, GABA-A; C059074:S 135; D012110:Reserpine; D003847:Deoxyglucose