Anticonvulsant Activity of Novel Derivatives of 2- and 3-Piperidinecarboxylic Acid in Mice and Rats

Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry

“…These metabolites were mainly increased 3-hydroxybutyric acid (BHBA) and nonesterified fatty acids (NEFAs), including palmitic acid (PA), heptadecanoic acid (HA), stearic acid (SA), trans-9-octadecenoic acid (T-9-OA), myristic acid (MA), cis-9-hexadecenoic acid (C-9-HA), which belong to the families of ketone bodies, long chain unsaturated fatty acids, and saturated acids [ 1 , 26 ], confirming that a great amount of fat mobilization resulting from hypoglycemia may cause ketosis. In addition, some up-regulated amino acids and their catabolic products, such as L-ile, a glucogenic and ketogenic amino acid [ 25 ]; Gly, biosynthesized from serine [ 27 ]; AMA, a constituent of proteins before hydrolysis [ 28 ]; and 2-piperidinecarboxylic acid (2PC), a metabolite of the lysine metabolism [ 29 ]; suggest that proteolysis increases to meet body energy demand in both CK and SK. Since 2PC up-regulation was highest in both CK and SK, it may play an important role in ketone body synthesis as a catabolic product of ketogenic lysine [ 29 ].…”

“…In addition, some up-regulated amino acids and their catabolic products, such as L-ile, a glucogenic and ketogenic amino acid [ 25 ]; Gly, biosynthesized from serine [ 27 ]; AMA, a constituent of proteins before hydrolysis [ 28 ]; and 2-piperidinecarboxylic acid (2PC), a metabolite of the lysine metabolism [ 29 ]; suggest that proteolysis increases to meet body energy demand in both CK and SK. Since 2PC up-regulation was highest in both CK and SK, it may play an important role in ketone body synthesis as a catabolic product of ketogenic lysine [ 29 ]. In addition, the up-regulation of other metabolites, such as 3-hydroxyvaleric acid (3HV), 3-hydroxy-3-methylglutaric acid (HMG), and AABA, implicated abnormal metabolic changes or functional abnormalities in both CK and SK, since high 3HV concentrations can be found in methylmalonic acidemia [ 30 ], increased HMG values may be caused by decreased coenzyme Q10 synthesis [ 31 ], and elevated AABA levels can be indicative of liver disease [ 32 ].…”

New Anticonvulsant Agents

“…The activity of several 2-piperidinecarboxyamides in the MES test in mice has been reported [85,86]. Receptor binding studies indicate that these amides demonstrated weak binding affinity at the phencyclidine (PCP) site on the N-methyl-D-aspartate (NMDA) receptor complex; however, a correlation between affinity and seizure protection in the MES test was not observed.…”

Anticonvulsant activities of 4-(4?-fluorophenoxy) benzaldehyde semicarbazone

“…Thus, two enaminones that were active in the corneal kindling screen did not protect against sei- chloride (55 mM) 10 100 ± 2 103 ± 2 89 ± 3* 101 ± 4 5 Veratridine 0.1 100 ± 2 108 ± 1* 114 ± 3* 117 ± 4* 6 (10 µM) (100 ± 2) (114 ± 1*) (114 ± 3*) (113 ± 3*) 1 100 ± 2 93 ± 3* 87 ± 6* 108 ± 4* 11 (100 ± 2) (87 ± 3*) (70 ± 8*) (102 ± 6) 10 100 ± 2 95 ± 2 76 ± 4* 113 ± 3* 8 (100 ± 3) (101 ± 3) (62 ± 7*) (115 ± 5*) zures in the amygdala kindling model when doses 6-10 times the ED 50 figures in the corneal test were used [Edafiogho et al, 1992;Scott et al, 1993]. Other examples may be cited, whereby doubling the ED 50 dose in the corneal kindling screen was required to give 20-50% control of seizures in the amygdala model [Hinko et al, 1996]. Nevertheless, the difference in activity displayed by Compound IV in the corneal and amygdala tests strongly suggests that protection in these two screens may occur by different mechanisms.…”