General pharmacological profile of the new cognition-enhancing agent nefiracetam.
The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)
Kitano
Y
Y
Drug Safety Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Makino
M
M
Usui
C
C
Takasuna
K
K
Kasai
Y
Y
Hirohashi
M
M
Tamura
K
K
Takayama
S
S
Kojima
H
H
Iizuka
H
H
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D002415:Cats; D002491:Central Nervous System Agents / Q000494:pharmacology; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000187:drug effects; D011619:Psychotropic Drugs / Q000097:blood / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000097:blood / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000187:drug effects
D002491:Central Nervous System Agents; D011619:Psychotropic Drugs; D011760:Pyrrolidinones; C058876:nefiracetam