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Biomedical subjects

N Narasimhachari

Publications and source records attributed to N Narasimhachari.

At least 19 recordsLinked to original sources
PubMed1990

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↗
PubMed1989

Relation of serum molindone levels to serum prolactin levels and antipsychotic response.

The antipsychotic drug molindone is considered to be atypical in its mode of action and to have mild side effects. Currently no data are available on the range of serum levels of this drug during treatment. By means of a high performance liquid chromatographic technique, serum molindone levels were measured in 14 psychotic patients receiving a wide range of doses of this drug. Molindone levels as high as 350 ng/mL were obtained and were not associated with any toxic effects. Significant relations were noted between the serum level of the drug and both serum prolactin level and treatment response. The authors suggest that molindone may have a range of serum levels consistent with therapeutic benefit. Serum molindone and prolactin levels might help assess resistance to molindone treatment.

Adult↗
PubMed1987

Activation of cortical tryptophan hydroxylase by acute morphine treatment: blockade by 6-hydroxydopamine.

Acute morphine produced a dose-dependent, naloxone-sensitive, reversible increase in tryptophan hydroxylase activity in low speed supernatants of midbrain, pons-medulla and cerebral cortex but not spinal cord. The increase in cortical enzyme activity was blocked by 6-hydroxydopamine pretreatment, could be reversed in vitro by incubation with alkaline phosphatase and was non-additive with the increase in enzyme activity induced in the presence of phosphorylating conditions. Morphine administration produced an increase in Vmax but no change in Km of cortical enzyme for substrate, tryptophan, or the artificial reduced pterin cofactor, 6-methyl-5,6,7,8-tetrahydropterin. The failure of morphine to increase spinal tryptophan hydroxylase activity despite enhancement of enzyme activity in medulla indicates regional differences in responsiveness of the enzyme to in vivo activation.

Alkaline Phosphatase↗
PubMed1986

Phencyclidine in CSF and serum: a case of attempted filicide by a mother without a history of substance abuse.

A previously healthy 30-year-old black woman with no history of substance abuse was hospitalized after she attempted to drown her 4-year-old son. She had become progressively confused and delusional after a flu-like illness 2 weeks before. Serum and lumbar CSF samples assayed for phencyclidine (PCP) by gas chromatography-mass spectrometry with d5 PCP as an internal standard were positive. The patient recovered rapidly after treatment with haloperidol and acidification of her urine. Suspicion of PCP abuse should remain high among patients with psychosis, even for those with no history of substance abuse.

Adult↗
PubMed1985

Posttraumatic stress disorder from pentaborane intoxication. Neuropsychiatric evaluation and short-term follow-up.

Fourteen individuals briefly exposed to a toxic industrial compound, pentaborane, were evaluated for neuropsychiatric abnormalities four to 12 weeks after exposure. Results of physical, neurological, and routine laboratory evaluations were normal. Initial and persistent psychiatric symptoms, neuropsychological deficits, electroencephalographic changes, elevated central nervous system neurotransmitter levels, and ventricular brain ratios (computed tomographic scan) provide evidence of central nervous system damage. Seven patients met diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, ed 3, for posttraumatic stress disorder, and seven patients had neuropsychological test evidence of mild brain dysfunction. No statistically significant relationship was found between neuropsychiatric test results and psychiatric diagnoses. These results contradict previous literature that reports most symptom resolution within the first week after exposure to pentaborane. Results suggest that patients suffered a combination of organic brain insult and psychological trauma.

Accidents, Occupational↗
PubMed1985

Effect of clonidine on the activity of tryptophan hydroxylase from rat brainstem following in vivo or in vitro treatment.

In vivo administration of clonidine hydrochloride (Catapres) via tail vein injection produced a rapid increase in brainstem tryptophan hydroxylase activity assayed in vitro under subsaturating conditions of reduced pterin cofactor, 6MPH4. Enzyme activity returned to and remained at control levels about 60 min after treatment with low doses of clonidine (5 micrograms/kg). However, with higher doses of the drug (15 micrograms/kg), enzyme activity fell to below control levels for about an hour. Incubation of brainstem slices with clonidine also produced a dose-dependent increase in enzyme activity. The increase in enzyme activity appears to be mediated indirectly since it was abolished when brain catecholamine levels were depleted by pretreatment with 6-hydroxydopamine 8 days prior to clonidine treatment. The kinetic properties of tryptophan hydroxylase prepared 25 and 90 min after clonidine administration indicate that the initial increase and subsequent decrease in enzyme activity seen under these conditions may be due to changes in apparent Vmax of the enzyme.

Animals↗
PubMed1985

Brain ventricular size and CSF monoamine metabolites in an adolescent inpatient population.

The cerebrospinal fluid monoamine metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA), were compared with ventricle-brain ratios (VBRs) in a group of adolescent inpatients who were divided into psychotic and nonpsychotic groups. HVA, 5HIAA, and VBR did not differ significantly between the two groups. There were no significant relationships between these variables in the nonpsychotic group. Psychotic adolescents, however, displayed significant negative correlations between VBR and HVA, and between VBR and 5HIAA. The relationship between VBR and monoamine metabolites appears to occur in psychoses other than schizophrenia, is present early in the course of illness, and probably does not represent a dilutional effect.

Adolescent↗
PubMed1985

Amphetamine response in borderline patients.

The behavioral and biological responses to d-amphetamine have been studied extensively in patients with schizophrenia and depression, and to a lesser degree in bipolar affective disorders. Because of theories linking borderline personality disorder to those illnesses, amphetamine, 30 mg, p.o., was administered to eight borderline patients in a double-blind, placebo-controlled study and the results were compared to the responses of normal subjects under identical conditions. Amphetamine led to symptoms of psychosis in four out of eight (50%) borderline patients. No normal subject became psychotic during the procedure. Global ratings of well-being were significantly elevated in the borderline group compared to the normal group. In addition the global response was highly inversely correlated with the patient's score on the Diagnostic Interview for Borderlines. Borderline patients had a nonsignificantly decreased growth hormone response following amphetamine compared to normals. Thus, borderline patients appear to be pharmacodynamically separable from normals.

Adult↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

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↗