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Biomedical subjects

N Narasimhachari

Publications and source records attributed to N Narasimhachari.

At least 19 recordsLinked to original sources

Identification of metabolites of 3,4-methylenedioxymethamphetamine in rats.

Liquid chromatography with electrochemical detection (LC/ECD) and gas chromatography/mass spectrometry (GC/MS) were used to identify metabolites of N-methyl-3,4-methylenedioxyamphetamine (MDMA) in samples of rat plasma and urine. Several potential metabolites, based on what is known about the metabolism of the desmethyl analog (i.e., MDA), were synthesized as standards to aid in the identification of the MDMA metabolites. MDA and N-methyl-1-(4-hydroxy-3-methoxy-phenyl)-2-aminopropane (3b) were identified in urine by HPLC and confirmed by GC/MS. 1-(4-Hydroxy-3-methyoxyphenyl)2-aminopropane, (3a), N-methyl-1-(3-hydroxy-4-methoxyphenyl)-2-aminopropane (2b) and 1-(3,4-dihydroxyphenyl)-2-aminopropane (4a) were tentatively identified by LC/ECD but insufficient sample size precluded confirmation by mass spectrometry. MDA was also identified in brain and plasma extracts. Because MDA is a metabolite of MDMA in humans, and because it has been speculated that the neurotoxic effects of MDA and MDMA may be due to a metabolite, the results of the present study may ultimately aid our understanding of the neurotoxic mechanism of these drugs of abuse.

3,4-Methylenedioxyamphetamine

Clonidine induced hyperphagia and weight gain in monkeys.

The effect of the alpha-noradrenergic receptor agonist, clonidine, on food intake and weight was examined in ten adult Stumptail macaque monkeys. An intramuscular injection of 0.1 mg/kg of clonidine HCl for seven consecutive days significantly increased food intake from baseline levels throughout treatment. All but two monkeys gained weight during clonidine treatment with seven animals gaining from 5--15% of their original body weight by the end of 1 week.

Animals

Interference by endogenous amines in the determination of monoamine oxidase activity of human platelet samples.

Lower monoamine oxidase (MAO) levels are reported in the blood platelets from chronic schizophrenics than in normal controls. Attempts to replicate these findings in other laboratories have been unsuccessful thus contradicting the suggestion that low MAO activity is a genetically determined biological factor in schizophrenia. We now present evidence to show that the endogenous amines present in platelets (serotonin) react non-enzymatically with the highly reactive aldehyde produced by MAO and thereby reduce the extractable radioactivity in the radiometric assays for MAO. Various biogenic amines such as serotonin, dopamine and m-tyramine were tested for their interference by adding them in nanomolar concentrations to incubation mixtures containing platelet samples or partially purified rat liver MAO and (14C-)p-tyramine or phenethylamine as substrates. The amines were added before, during and after incubation. In all three cases the apparent inhibition by each amine was the same, the percent inhibition depending on the structure of the amine.

Acetaldehyde

Simultaneous determination by GC-MS-SIM of o-, m-, p-hydroxyphenylacetic acid, 3:4-dihydroxyphenylacetic acid and homovanillic acid in biological samples using a common selected ion.

A GC-MS-SIM method is described for the simultaneous determination of five acid metabolites, o-, m-, and p-hydroxyphenylacetic acid, 3:4-dihydroxyphenylacetic acid and homovanillic acid in biological samples using a common selected ion for all the acids. The TMS ethers of methyl or ethyl esters of these compounds have a common ion at m/e 179 which is used for their quantitation by selected ion monitoring. The molecular ion at m/e 238 of the three monohydroxy phenylacetic acids, which is also the M-30 ion for homovanillic acid, is also used for their quantitation. The GC conditions for their separation, the relative sensitivities and some advantages of TMS ethers over other derivatives are described. The application of this method to biological samples is illustrated by data on human urine and plasma.

3,4-Dihydroxyphenylacetic Acid

Selective introduction of TMS groups in tryptamines: preparation of N1-TMS derivatives of tryptamines.

Indolethylamines (tryptamines) with a primary animofunction react with Regisil under controlled conditions to yield a mono TMS derivative. Mass spectrometry to these derivatives shows that the TMS group is substituted on the indolic nitrogen (N1) and not the primary amino nitrogen. This is confirmed by converting these compounds to their isothiocyanate derivatives. The GC and GC-MS data of some typical compounds are presented.

Amino Acids

Plasma indolethylamine-n-methyltransferase activity and growth hormone level during sleep: a pilot study.

Polygraphic recordings and sequential growth hormone (GH) samplings were performed in eight healthy adult males. In the plasma samples from seven of the subjects, indolethylamine-N-methyltransferase (INMT) activity was also determined. Five of eight subjects showed significant fluctuation in plasma GH level, and six of seven subjects showed significant fluctuation in plasma INMT activity level. There were also significant positive correlations between plasma GH and INMT activity level during the second episode of NREM sleep stage 1 and during the third episode of NREM sleep stage 2. A significant negative correlation between plasma GH and INMT activity level during the seventh episode of sleep stage 2 and during the fifth episode of post sleep-onset wake was found. In view of a previous finding that INMT activity in the serum of psychiatric patients is positively correlated with severity of delusions, the observation that NREM sleep is associated with mental activity characterized by repetitive thoughts, and the result that GH level in plasma is increased in NREM sleep early at night, our present findings suggest the hypotheses that increased plasma INMT activity during sleep is indicative of both increased INMT activity in the central nervous system (CNS) and the activation or maintenance of NREM mental activity during sleep. Additional research will be needed in order to validate our observations and test these hypotheses.

Adult

Immunoglobulin levels in psychiatric patients.

In a study of 19 schizophrenic patients, 7 nonschizophrenic patients, and 31 controls, the authors found significantly higher mean serum levels of 1) immunoglobulin A in schizophrenic women then in control women and in schizophrenic blacks than in either schizophrenic whites or black controls. 2) immunoglobulin D in schizophrenic blacks than in schizophrenic whites, 3) immunoglobulin M in controls than in nonschizophrenic patients, and 4) immunoglobulin G (IgG) in schizophrenics whose urine was positive for phenothiazines than in schizophrenics whose urine was negative for phenothiazines. High serum levels of IgG were associated with no or mild hallucinations and low levels with moderate or severe hallucinations. Black female patients had significantly more severe hallucinaions than white female patients. The authors discuss the possible implications of these findings.

Black People

Structure-activity relationships among desmethyl derivatives of neuroleptics and antidepressants for substrate specificty to indolethylamine N-methyltransferase from rabbit lung.

Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation.

Animals

The simultaneous determination by selected ion monitoring of the levels of homovanillic, isohomovanillic, 3,4-dihydroxyphenylacetic and 3-methoxy-4-hydroxymandelic acids in single biological samples.

Methods for the determination and quantitation of homovanillic, isohomovanillic, 3,4-dihydroxyphenylacetic and 3-methoxy-4-hydroxymandelic acids in single samples of biological material by gas chromatography, gas chromatographic mass spectrometry and selected ion monitoring during gas chromatographic mass spectrometry are described. Examples of the levels of these four acid metabolites of catecholamines in serum and CSF of untreated dog, cat and human, in urine of parkinsonian subjects treated with varying doses of L-DOPA and in CSF of dogs which had received 1 g of L-DOPA per day for 7 weeks are presented.

3,4-Dihydroxyphenylacetic Acid

Tetrahydrofolic acid: an inhibitor of the methyltetrahydrofolic acid-mediated methylation of indolethylamines.

Tetrahydrofolic acid exerts a product inhibition on the methyltetrahydrofolic acid-mediated methylation of indolethylamines. Kinetic studies showed that this inhibition was competitive with respect to methyltetrahydrofolic acid and non-competitive with respect to N-methylserotonin. Chromatographic separation of S-adenosylmethionine-dependent indolethylamine N-methyltransferase and methyltetrahydrofolic acid-dependent methyltransferase from rabbit lung was obtained. There was no cross reaction of the two enzymes to tetrahydrofolic acid, S-adenosylhomocysteine, N, N-dimethyltryptamine or bufotenin.

Adenosine