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Biomedical subjects

N Chatterjie

Publications and source records attributed to N Chatterjie.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis of valproic acid amides of a melatonin derivative, a piracetam and amantadine for biological tests.

Three new amide derivatives of valproic acid have been synthesized and characterized by spectrophotometric studies. The rationale for the preparation of such agents has been based on the observation that chemical combination of the anticonvulsant pharmacophore, valproic acid with amine moieties produces more effective and less toxic amides. The amine components selected in this work also exhibit neuroactivity with the prospect of these agents being biologically active in controlling not just seizures and but also possessing neuroprotective properties. We report here the synthesis and properties of the valproylamides of 5-methoxytryptamine, related to melatonin (1), of N-substituted 2-pyrrolidinone related to piracetam (2), and of adamantylamine related to amantadine (3). In preliminary tests these compounds showed low toxicity and a variety of anticonvulsive properties, including a delay in onset of activity. These compounds and their derivatives are now available to be tested additionally for control of subclinical seizures, enhancement of cognition, behavior modification and alleviation of symptoms and disorders due to neuronal damage.

Amantadine↗
PubMed1998

Dextro-naloxone counteracts amphetamine-induced hyperactivity.

The locomotor stimulating effect of d-amphetamine in mice was counteracted by the administration of l-naloxone [(-)-naloxone], a known opiate receptor antagonist. Mice injected with amphetamine reached a peak locomotor activity within 30 min. When treated simultaneously with amphetamine and l-naloxone, these subjects showed low motility. Furthermore, when mice were treated not with l-naloxone but with its mirror image, d-naloxone [(+)-naloxone], a compound that by itself does not antagonize opiates and does not affect spontaneous motility, they showed no amphetamine-induced hyperactivity. The finding that an enantiomer of naloxone, with no opiate antagonist activity, is able to block the excitatory action of amphetamine, suggests the existence of a hitherto unknown mechanism of counteracting some of the effects of stimulants and euphoriants like amphetamine and cocaine.

Amphetamine↗
PubMed1996

Prevention of cocaine-induced hyperactivity by a naloxone isomer with no opiate antagonist activity.

Dextro-naloxone [(+)-naloxone], an isomer with almost no opiate antagonist activity and no effect on spontaneous locomotor activity, can reduce cocaine-induced hyperactivity in mice. The classical opiate antagonist, levo-naloxone [(-)-naloxone], is known to counteract the excitatory motor effects of amphetamine and cocaine, but it has been tacitly assumed that this action of levo-naloxone is dependent on its ability to antagonize endogenous opioids. Our finding that a naloxone isomer with little or no opioid antagonist activity is also able to inhibit the cocaine effect on spontaneous motility, calls for a reconsideration of this assumption.

Animals↗
PubMed1992

Gln-41 is intermolecularly cross-linked to Lys-113 in F-actin by N-(4-azidobenzoyl)-putrescine.

The bifunctional reagent N-(4-azidobenzoyl)-putrescine was synthesized and covalently bound to rabbit skeletal muscle actin. The incorporation was mediated by guinea pig liver transglutaminase under conditions similar to those described by Takashi (1988, Biochemistry 27, 938-943); up to 0.5 M/M were incorporated into G-actin, whereas F-actin was refractory to incorporation. Peptide fractionation showed that at least 90% of the label was bound to Gln-41. The labeled G-actin was polymerized, and irradiation of the F-actin led to covalent intermolecular cross-linking. A cross-linked peptide complex was isolated from a tryptic digest of the cross-linked actin in which digestion was limited to arginine; sequence analysis as well as mass spectrometry indicated that the linked peptides contained residues 40-62 and residues 96-116, and that the actual cross-link was between Gln-41 and Lys-113. Thus the gamma-carboxyl group of Gln-41 must be within 10.7 A of the side chain (probably the amino group) of Lys-113 in an adjacent actin monomer. In the atomic model for F-actin proposed by Holmes et al. (1990, Nature 347, 44-49), the alpha-carbons of these residues in adjacent monomers along the two-start helices are sufficiently close to permit cross-linking of their side chains, and, pending atomic resolution of the side chains, the results presented here seem to support the proposed model.

Actins↗
PubMed1989

Naloxone-6 alpha-spirohydantoin: a long-acting opiate antagonist.

We have synthesized a novel derivative of naloxone, naloxyl-6 alpha-spirohydantoin. The compound was rigorously purified and its stereochemical structure characterized. In tests in vivo in mice, it was less toxic than the parent compound and it showed weak anticonvulsive activity. It exerted antagonist effects comparable to those of naloxone but its effects were longer lasting, persisting for a week.

Animals↗
PubMed1989

Prevention of hyperthermia-induced seizures in immature rats by a hydantoin derivative of naloxone.

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Animals↗
PubMed1989

A spirohydantoin derivative of oxymorphone: an agonist with delayed antagonist activity.

We have synthesized a novel derivative of oxymorphone, oxymorphone-6 alpha-spirohydantoin. The derivative was less toxic in mice than the parent compound and it showed a significant anticonvulsive activity. It exerted agonist effects in doses lower than those of morphine and its agonist effects were longer lasting. Furthermore, both oxymorphone and the 6-spirohydantoin showed definite antagonist properties 48 hr later: they prevented analgesic effects of morphine. The antagonist effects of the derivative persisted for a week.

Analgesia↗
PubMed1986

Anticonvulsant properties of spirohydantoins derived from optical isomers of camphor.

Natural camphor exists as the d (+) form but the l (-) form has been synthesized. Replacement of the keto group on carbon 2 of each form with a hydantoin moiety led to only one spirohydantoin derivative. Both d and l derivatives were synthesized. Both forms and their racemic mixture were tested in vivo for toxicity and behavioral effects in mice. A dose of 100 mg/kg of the d form was not toxic: mice showed normal grooming and exploratory behavior; the l form induced hunched posture, body jerks and myoclonic manifestations followed by quiescence. The dl form showed intermediate effects. Challenge with the convulsant pentylenetetrazol (Metrazol) 2 hr after treatment with placebo or the camphor spirohydantoins produced seizure manifestations in all controls, in half of the subjects pretreated with the d-camphor derivative, in none of those pretreated with the l derivative and an intermediate response in those pretreated with racemic mixture. Thus, a spirohydantoin moiety added to camphor conferred strong anticonvulsive properties on the l form and modest ones on the d form; the d form did not seem to antagonize the l form.

Animals↗
PubMed1985

Convulsive thresholds in mice: action of 6-hydroxydopamine and eboracin.

The neurotoxin, 6-hydroxydopamine, when injected intraperitoneally, protected mice from seizures induced by pentylenetetrazol (Metrazol) and altered the nature of the convulsive response induced by an auditory stimulus. Conversely, the indenopyrrole, eboracin, protected mice from seizures induced by auditory stimulation and altered the response to Metrazol. In each case the altered response was characterized by a marked prolongation of the clonic component without progression to the generalized tonic phase. It appeared, therefore, that 6-hydroxydopamine raised the threshold to tonus in audiogenic seizures, and eboracin raised it in Metrazol seizures. Eboracin raised threshold to clonic phase in audiogenic seizures whereas 6-hydroxydopamine raised it in Metrazol seizures. Our findings showed that in Metrazol and audiogenic seizures thresholds to clonus and progression to the tonic phase were mediated by different biochemical mechanisms and suggested that agents controlling induction of clonic manifestations in one seizure model may be those involved in controlling seizure spread in the other.

Acoustic Stimulation↗
PubMed1985

Comparison of anticonvulsive properties of eboracin and phenytoin in mice.

The in vivo effects of phenytoin (diphenylhydantoin, Dilantin) and the experimental anticonvulsant, eboracin, a substituted indenopyrrole, were compared in mice. Pretreatment with varying dosages of either agent followed by challenge with the chemoconvulsant pentylenetetrazol (Metrazol) indicated that eboracin provided slightly less protection against seizures than phenytoin and was much less toxic. Intermediate doses of either agent led to a form of clonic status epilepticus which persisted for an average of 18 min in phenytoin-treated and 58 min in eboracin-treated mice. Pretreatment with higher or lower doses did not lead to these manifestations. Animals in which this syndrome had been induced should be of value in studies of the chemistry and physiology of the clonic state.

Animals↗
PubMed1982

Eboracin: a substituted indenopyrrole active against metrazol-induced, audiogenic and electroshock seizures in mice.

1. Pretreatment with eboracin, a methyl ester of a trioxyindenopyrrole, inhibited the tonic phase of pentylenetetrazol (Metrazol)-induced, audiogenic and electroshock seizures in mice. 2. In animals challenged with Metrazol a dose of 28 mg/kg eboracin prevented 50% of tonic-clonic responses. 3. In animals exposed to electroshock or auditory stimulation the dose required to produce a 50% reduction in tonic-clonic seizures was 30 mg/kg and 35 mg/kg, respectively. 4. The 50% lethal dose was 832 mg/kg, indicative of eboracin's relatively low toxicity and high therapeutic index. 5. Pretreatment with eboracin led to a prolongation of the myoclonic phase of Metrazol seizures, similar to that observed after phenytoin.

Acoustic Stimulation↗
PubMed1982

Effect of eboracin on convulsive seizures in mice: enhancement of myoclonus and inhibition of the tonic phase.

Eboracin, a substituted trioxyindenopyrrole, inhibited the tonic component of convulsive seizures induced in mice by pentylenetetrazol, electroshock or auditory stimulation. Single doses decreased the incidence of tonic-clonic seizures (ED50=28-35 mg/kg); complete inhibition of tonus followed doses of 40-150 mg/kg. A dose of 75-150 mg/kg of eboracin prolonged the duration and increased the severity of the myoclonic component of seizures induced by pentylenetetrazol.

Acoustic Stimulation↗
PubMed1980

Structural elucidation of adducts formed by ninhydrin with indoles and thiourea by 13C-NMR spectroscopy.

Condensation products were prepared by the reaction of ninhydrin with indole and 2,5-dimethylindole. The structures of these 1:1 adducts were assigned as 3-(2-hydroxy-2-indane-1,3-dionyl)indole and 3-(2-hydroxy-2-indane-1,3-dionyl)-2,5-dimethylindole, respectively, on the basis of spectral data including 13C-NMR evidence. 13C-NMR also was used to confirm the structure of a thiourea-ninhydrin adduct as a substituted thioindeno[1,2-d]imidazole-2,8-dione.

Carbon Isotopes↗
PubMed1980

Anticonvulsive activity of indenoimidazolidinones and related heterocyclic compounds in mice.

A series of substituted cyclic ureides and related compounds, one of them a thio analog, were synthesized by condensing ninhydrin with urea, thiourea, dimethylurea or other aromatic or bifunctional agents. When tested against seizures induced in mice by the chemoconvulsant Metrazol or against audiogenic seizures, four compounds decreased either the incidence or the severity of convulsive manifestations and protected from mortality in seizures. The effective compounds were not toxic at the administered level (150 mg/kg) and produced few observable sedative effects.

Acoustic Stimulation↗