Protective action of nicotinic acid benzylamide in a variety of chemically-induced seizures in mice.

Purpose: The study aims to assess the anticonvulsant effects offered by benzylamide nicotinic acid (Nic-BZA) in many animal models of chemically-induced seizures (i.e., pentylenetetrazole [PTZ], pilocarpine [PILO], bicuculline [BIC], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], kainic acid [KA], and N-methyl-d-aspartic acid [NMDA]).

Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model.

Purpose: The aim of this study was to assess the anticonvulsant potency of 6 various benzylamide derivatives [i.e., nicotinic acid benzylamide (Nic-BZA), picolinic acid 2-fluoro-benzylamide (2F-Pic-BZA), picolinic acid benzylamide (Pic-BZA), (RS)-methyl-alanine-benzylamide (Me-Ala-BZA), isonicotinic acid benzylamide (Iso-Nic-BZA), and (R)-N-methyl-proline-benzylamide (Me-Pro-BZA)] in the threshold for maximal electroshock (MEST)-induced seizures in mice.

New potential renin inhibitors with dipeptide replacements in the molecule.

A series of eight non-peptidic potential renin inhibitors have been designed and synthesized. All of them contain dipeptide replacement: (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) in their molecules. Four among them comprise two additional analogs of dipeptide: (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta).

New derivatives of benzylamide with anticonvulsant activity.

Previously obtained picolinic acid benzylamide is a potent anticonvulsant with low neurotoxicity. In search for new effective anticonvulsants twelve new benzylamides (1-12) were synthesized and preliminary evaluated in the Anticonvulsant Screening Program (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Two of them appeared the most promising: 1-cyclopentenecarboxylic acid benzylamide (1-Cpc-BZA) (9) showed MES ED50 = 85,36 mg/kg (PI = 2,49), scPTZ ED50 = 1,37 mg/kg (PI = 1,37), 6Hz-EST ED50 = 50,29 mg/kg and cyclopentanecarboxylic acid benzylamide (Cpc-BZA) (11) showed pilocarpine ED50 = 154.