Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3-acylamino lactams.
A series of 3-(acylamino)-epsilon-caprolactams and 3-(acylamino)-2-pyrrolidinones was synthesized. Some of these compounds reversed at different degrees electroconvulsive shock- and Scopolamine-induced amnesia, using a step-through passive avoidance in mice. Classical nootropic drugs, i.e., Aniracetam, Oxiracetam, and Piracetam, were used as reference compounds. Within the analyses of data performed, we introduced a new parameter, the confrontation index (CI), which is a function of Mann-Whitney's U statistic. The CI permits a common scale of activity of substances to be generated, independently of probabilistic hypotheses, with higher scores representing higher activities. The most active compounds were characterized by the formylamino and [3-(trifluoromethyl)benzoyl]amino groups in the 3-position of the ring. None of the substances assayed showed any effect on spontaneous behavior and neurovegetative system.
Istituto di Farmacologia II, Università di Roma La Sapienza, Italy.
L
L
Angelucci
P
P
Calvisi
R
R
Catini
U
U
Cosentino
R
R
Cozzolino
P
P
De Witt
O
O
Ghirardi
F
F
Giannessi
A
A
Giuliani
D
D
Guaraldi
D000647:Amnesia / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D015195:Drug Design; D004597:Electroshock; D066298:In Vitro Techniques; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011619:Psychotropic Drugs / Q000138:chemical synthesis* / Q000494:pharmacology; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012601:Scopolamine; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D007769:Lactams; D011619:Psychotropic Drugs; D011760:Pyrrolidinones; D012601:Scopolamine