1. Anxiolytic properties of 1-aminocyclopropanecarboxylic acid, a ligand at strychnine-insensitive glycine receptors
P Skolnick, R Trullas, B Jackson Pharmacol Biochem Behav . 1989 Oct;34(2):313-6. doi: 10.1016/0091-3057(89)90317-1.
The effects of 1-aminocyclopropanecarboxylic acid were investigated on performance in an elevated plus-maze. This compound is a high-affinity, partial agonist ligand at strychnine-insensitive glycine receptors of the N-methyl-D-aspartate receptor complex. Like chlordiazepoxide, 1-aminocyclopropanecarboxylic acid increased in a dose-dependent manner both the percent entries into and the percent time spent in the open arms of the plus-maze. However, 1-aminocyclopropanecarboxylic acid was significantly less efficacious than chlordiazepoxide in these measures and increased, while chlordiazepoxide decreased, the time spent in the middle platform of the plus-maze. These findings indicate that ligands acting through strychnine-insensitive glycine receptors on the N-methyl-D-aspartate receptor complex may represent a new class of anxiolytic agents with a profile which differs from the benzodiazepines.
2. 1-Aminocyclopropanecarboxylic acid: mouse to man interspecies pharmacokinetic comparisons and allometric relationships
S C Cherkofsky J Pharm Sci . 1995 Oct;84(10):1231-5. doi: 10.1002/jps.2600841016.
1-Aminocyclopropanecarboxylic acid (ACPC) is a partial agonist at the strychnine-insensitive glycine recognition site on the N-methyl-D-aspartate (NMDA) receptor complex in the mammalian central nervous system with preclinical activity in animal models of neuroprotection and psychiatric illnesses. The pharmacokinetics of ACPC were studied in the rat, beagle dog, cynomolgus monkey, and human, and compared also with data from the literature for the mouse. Plasma elimination half-lives were 1.5, 2.5, 2.9, 20.3, and 5.9 h for the mouse, rat, monkey, dog, and human, respectively. Volume of distribution at steady state (0.74 L/kg) was constant across all species. Clearance values were consistent with glomerular filtration rates for all species, except in the dog, where clearance is consistent with 84% tubular reabsorption. Allometric relationships for clearance and half-life versus body weight confirmed the predictability of the pharmacokinetics of ACPC in the mouse, rat, monkey, and human. Continued clinical evaluation of ACPC as a neuroprotective agent and in a variety of psychiatric illnesses is warranted.
3. The singular gas-phase structure of 1-aminocyclopropanecarboxylic acid (Ac3c)
Carlos Cabezas, José L Alonso, Juan C López, Carlos Cativiela, Vanesa Vaquero, Ana I Jiménez J Am Chem Soc . 2011 Jul 13;133(27):10621-8. doi: 10.1021/ja2033603.
The natural nonproteinogenic α-amino acid 1-aminocyclopropanecarboxylic acid (Ac(3)c) has been vaporized by laser ablation and studied in the gas phase by molecular-beam Fourier transform microwave spectroscopy. Comparison of the experimental rotational and (14)N nuclear quadrupole coupling constants with the values predicted ab initio for these parameters has allowed the unambiguous identification of three Ac(3)c conformers differing in the hydrogen bonding pattern. Two of them resemble those characterized before for the coded aliphatic α-amino acids. Remarkably, a third conformer predicted to be energetically accessible for all of these amino acids but never observed (the so-called "missing conformer") has been found for Ac(3)c, close in energy to the global minimum. This is the first time that such a conformer, stabilized by an N-H···O(H) hydrogen bond, is detected in the rotational spectrum of a gaseous α-amino acid with a nonpolar side chain. The conjugative interaction established between the cyclopropane ring and the adjacent carbonyl group seems to be responsible for the unique conformational properties exhibited by Ac(3)c.
