HPLC determination of brain biogenic amines following treatment with bispyridinium aldoxime K203.

Effect of a new acetylcholine-esterase reactivator, K203 as a new potential antidote in organophosphate intoxications was studied on dopamine (DA), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in seven brain regions (cerebellum, spinal cord, hippocampus, hypothalamus, striatum, medulla oblongata and frontal cortex) of rats by an optimized and validated HPLC method. No significant change in brain level of these neurotransmitters was found either 15 or 60 min following treatment. However, when 5-HIAA/5-HT ratios were calculated as measure of turnover, significant decreases were found in the cerebellum, hippocampus, hypothalamus and the frontal cortex 15 min following K203 administration, but after 60 min only in the frontal cortex.

Medicinal chemistry of antimigraine drugs.

Migraine is one of the most frequent neurological disorder with high impact on the quality of life. Primary headaches such as migraine are pathophysiologically complex disorders. The concept of the trigeminovascular system dysfunction in migraine has led to a number of drug discoveries dramatically changing the treatment options.

Antioxidants in organophosphorus compounds poisoning.

Oxidative stress has recently been implicated as a factor in the mortality and morbidity induced by organophosphorus (OP) compound poisoning. An overwhelming number of research papers are based on studying at the cellular and organ level. Such studies have concluded that antioxidants can be used as an adjunct compound in the treatment of both chronic as well as acute OP poisoning.

Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the biogenic amine level of the adult rat brain: could oxytocin-induced labor cause pervasive developmental diseases?

Perinatal single-hormone treatment causes hormonal imprinting with lifelong consequences in receptor-binding capacity, hormone production as well as in social and sexual behavior. In the present experiments, newborn rats were treated with a single dose of oxytocin, and the levels of biogenic amines and their metabolites were studied in 8 different brain regions and in the sera when the male and female animals were 4 months old. Both dopaminergic and serotonergic neurotransmission was found to be significantly influenced.

Study on medicinal chemistry of K203 in wistar rats and beagle dogs.

K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase reactivator of potential use in organophosphate/ organophosphonate poisoning. Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion-pair HPLC. Serum and cerebrospinal fluid concentrations of K203 were determined using ion-pair reversedphase chromatography on octadecyl silica column.

Prodrugs and active metabolites among antidepressive compounds.

Clinical effect of drugs is influenced by the composition of the pharmaceutical preparation but substantially by the fate of the drug in the body. Metabolism of the xenobiotic drug compounds may result in pharmacologically inactive metabolites, however, metabolites with higher pharmacological activity can also be produced. These active metabolites may have different pharmacokinetic properties than the parent drug.

Effect of perinatal stress on the biogenic amine neurotransmitter level of the adult rat's brain.

The amount of biogenic amines (dopamine and serotonin) and their metabolites (DOPAC, HVA, 5-HIAA, and 5-HTOL) in five regions of the brain (frontal cortex, hypothalamus, hippocampus, striatum, and brainstem) was studied in the male and female offspring of control and perinatally (48 h before birth or 48 h after birth) food and water deprived dams, when they were three months old, by using HPLC-EC determination. The increase of amine or metabolite level was dominant (19 values increased and 10 decreased related to control). Before-birth stress caused increase in 9 case and only 2 decreased, while in the case of after-birth stress 10 increased and 8 decreased.

Pyridinium aldoxime analysis by HPLC: the method for studies on pharmacokinetics and stability.

Reversed-phase separation of various pyridinium aldoximes requires a certain concentration of ion-pairing agent, as their chemical structures contain two quaternary amines in the pyridinium ring. Adequate mobile phase is scouted on the basis of retention of pyridinium aldoxime (using the graph of k' versus concentration of an ion-pairing agent) compared to the chromatogram of the background peaks originated from the homogenate. Change in the ion-pairing agent concentration was more expressed for the elution of K-203 than that of the background peaks from the serum, brain and cerebrospinal fluid.

Monitoring by HPLC of chamomile flavonoids exposed to rat liver microsomal metabolism.

Three major flavonoid chamomile components (quercetin, apigenin-7-O-glucoside and rutin) were subjected to oxidative metabolism by cytochrome P-450 of rat liver microsomal preparations. Changes over time in their respective concentrations were followed using reversed-phase HPLC with UV detection. No clean-up had to be applied as only the specific flavonoid had to be separated from the background components originating from the rat liver microsome.