Central Nervous System Agents Research Articles

Derivatives of 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine as central nervous system agents.

Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an antidepressant against tetrabenazine depression and as a neuroleptic as measured by protection vs. amphetamine lethality in grouped mice.

Tetracyclic heterocycles as CNS agents

AbstractA considerable number of new tri and tetracyclic heterocycles (II) and open chain intermediates were synthesized. These were tested in a battery of assays designed to reveal central nervous system (CNS) activity. However, none showed useful activity greater than known analogs.

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 5. Conformationally mobile analogues derived by furan ring opening.

Synthesis and antitetrabenazine activity of 4-[2-(arylmethyl)phenyl]piperidines and 4-(benzyloxy)-4-phenylpiperidines, prepared as simplified and possibly more readily synthesized analogues of 3-phenylspiro[isobenzofuran-1 (3H),4'-piperidine], are reported. Several 4-[2-(arylmethyl)phenyl]piperidines display antitetrabenazine activity comparable to imipramine or amitriptyline but are two- to fourfold less active than analogous 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Structure--activity relationships for 4-[2p(arylmethyl)phenyl]piperidines are generally similar to the profile established for 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Significant antitetrabenazine activity is associated only with derivatives where the arylmethyl group is ortho to the piperidine ring. 4-(Benzyloxy)-4-phenylpiperidines and 4-[2-(arylmethyl)phenyl]-4-piperidinols and the corresponding methyl ethers and esters display weak to modest antitetrabenazine activity. 4-[2-(Arylmethyl)phenyl]-1,2,3,6-tetrahydropyridine derivatives, at best, exhibit modest antitetrabenazine activity, with the exception of 4-[2-(phenylmethyl)phenyl]-1,2,3,6-tetrahydropyridine which is approximately equipotent with amitriptyline. The results of these investigations allow certain speculations to be made with respect to the role of the furan ring in the 3-arylspiro[isobenzofuran-1(3H),4'-piperidines] and antitetrabenazine activity.

Behavioral toxicology of carbon disulfide and toluene.

Organic solvents are pervasive in the communal and industrial environments. Although many are potent central nervous system agents, clearly delineated behavioral effects have played only a minor role in the formation of exposure standards. A comprehensive behavioral pharmacology and toxicology of these compounds is one aim of US/USSR collaboration. The current report describes some actions of carbon disulfide and toulene. Earlier data about the actions of carbon disulfide on pigeon operant performance indicated disruption of schedule-controlled key-pecking. Primate data are now described from a situation designed to determine aversive thresholds to electrical stimulation. Effective concentrations of carbon disulfide produced both a rise in the amount of electric shock tolerated and a diminution of the response force exerted by the monkeys. In experiments with toluene, pigeons were shown to elevate key-pecking rate in an operant situation at certain concentrations. Toluene also was studied for its capacity to maintain self-administration in the same way as drugs of abuse. Monkeys worked to gain access to toulene vapor just as they work for opiates or amphetamines. The current experiments demonstrate how comprehensive the range of behavioral toxicology needs to be to deal with environmental health issues.

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants.

The synthesis of 1'-[3-(4-fluorobenzyoyl)propyl]-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (2a) and eight halo and methoxy analogues is described. The compounds were generally more potent per os than chlorpromazine in the Sidman avoidance paradigm in rats and less potent than haloperido. 1'-[3-(4-Fluorobenzoyl)propyl]-3-(4-fluorophenyl)spiro[isobenzofuran-1(3H),4'-piperidine] (2e) approached the per os potency of haloperidol in this test and was shown to be active in inhibiting monkey avoidance also. Compound 2e was much less active than haloperidol in antagonizing apomorphine-induced emesis in dogs, apomorphine-induced stereotypy in rats, and amphetamine-induced circling in lesioned rats. This lack of nonselective, dopamine-receptor blocking effects makes 2e attrative as a potential neuroleptic.

2-Pyrrolidinylideneureas, a new class of central nervous system agents.

A series of N-aryl-N'-(1-methyl-2-pyrrolidinylidene)ureas was prepared and screened for pharmacological activity. Congeners possessing either phenyl or phenyl substituted with 4-nitro, 3-bromo, 3-chloro, 3-fluoro, and 3-methyl groups were found to demonstrate anxiolytic activity. 2,6-Disubstitution of the phenyl ring with methyl, chloro, and bromo imparted potent muscle-relaxant properties which appear to be centrally mediated. A significant separation of the anxiolytic and muscle-relaxant properties from other CNS activities, e.g., anticonvulsant, sedative, and hypnotic, was achieved.

3-Aminotetrahydrocarbazoles as a new series of central nervous system agents

3-Dimethylamino-1,2,3,4-tetrahydrocarbazole, a structurally modified tryptamine, prevented amphetamine-induced stereotyped behavior in rats and prevented reserpine-induced ptosis in mice. Further study of this compound and a number of substituted derivatives indicated that either imipramine-like or chlorpromazine-like profiles were obtainable by changing substituents and their positions.

Partly reduced biphenyls as cetral nervous system agents. 3. Cis- and trans-4-aryl-4-methoxycyclohexylamines.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPartly reduced biphenyls as central nervous system agents. 3. cis- and trans-4-Aryl-4-methoxycyclohexylaminesDaniel Lednicer, D. Edward Emmert, Robert Lahti, and Allan D. RudzikCite this: J. Med. Chem. 1973, 16, 11, 1251–1256Publication Date (Print):November 1, 1973Publication History Published online1 May 2002Published inissue 1 November 1973https://doi.org/10.1021/jm00269a008RIGHTS & PERMISSIONSArticle Views79Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (532 KB) Get e-Alerts Get e-Alerts

Partly reduced biphenyls as central nervous system agents. 1. 4-Arylcyclohex-3-enylamines.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPartly reduced biphenyls as central nervous system agents. 1. 4-Arylcyclohex-3-enylaminesDaniel Lednicer, D. Edward Emmert, Robert Lahti, and Allan D. RudzikCite this: J. Med. Chem. 1972, 15, 12, 1235–1238Publication Date (Print):December 1, 1972Publication History Published online1 May 2002Published inissue 1 December 1972https://doi.org/10.1021/jm00282a008RIGHTS & PERMISSIONSArticle Views88Altmetric-Citations5LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (468 KB) Get e-Alerts Get e-Alerts

Partly reduced biphenyls as central nervous system agents. 2. cis- and trans-4-Arylcyclohexylamines.

Partly reduced biphenyls as central nervous system agents. 2. cis- and trans-4-Arylcyclohexylamines.

Central nervous system agents. 4. Analogs of 3-amino-2-phenylpropiophenone.

Central nervous system agents. 4. Analogs of 3-amino-2-phenylpropiophenone.

Central nervous system agents. 1. Synthesis of diphenyl-tert-aminopropanols.

Central nervous system agents. 1. Synthesis of diphenyl-tert-aminopropanols.

Central nervous system agents. 2. Synthesis of diphenyl primary and secondary aminopropanols.

Central nervous system agents. 2. Synthesis of diphenyl primary and secondary aminopropanols.

Central nervous system agents. 3. Structure-activity relationship of a series of diphenylaminopropanols.

Central nervous system agents. 3. Structure-activity relationship of a series of diphenylaminopropanols.

A new class of 1,3-benzoxazinones as potential cetral nervous system agents.

A new class of 1,3-benzoxazinones as potential cetral nervous system agents.

Magnesium pemoline: enhancement of brain RNA polymerases.

The stimulation by magnesium pemoline of systems that synthesize brain nucleic acid was studied in vivo and in vitro. There are differential effects between true RNA polymerase and pseudo-RNA polymerase. The selective stimulation of true RNA polymerase by magnesium pemoline was not observed with stimulants of the central nervous system and psychotropic agents.

The effect of central nervous system agents on rat-brain γ-aminobutyric acid level

γ-Aminobutyric acid has been implicated as a central nervous system neurohumoral depressant by a number of investigators. The hypothesis that brain excitability is inversely proportional to the γ-aminobutyric acid content was tested with compounds that were reported active by others and with a number of central nervous system stimulants and depressants. Of twelve compounds tested, e.g., ethanol, hydroxylamine, pentylenetetrazol and phenobarbital, none produced dramatic changes in rat-brain γ-aminobutyric acid content. It was concluded that the presence of γ-aminobutyric acid in central nervous system tissue alone does not imply a physiological role a priori.

Presence of two interrferring enterovirral agents (ECHO virus type 9 and poliovirus type 2) in the human central nervous system.

A cytopathogenic and suckling-mouse pathogenic agent isolated from the CNS of an infant appeared to consist essentially of two different interfering viruses. The major component was ECHO-9 virus, the minor component was polio virus type 2. Both viruses were segregated by various methods: (1) cultivation in human papilloma cells, in which only the poliovirus multiplied, (2) plating of high dilutions of monkey kidney culture fluid, which yielded ECHO-9 single plaque progeny, (3) suckling-mouse passage. Poliomyelitis-like lesions developed after intracerebral and intraspinal inoculation of monkey kidney culture fluid containing both components, but only in monkeys that had been treated with cortisone. The CNS of these monkeys yielded mostly ECHO-9 virus, and occasionally poliovirus type 2. ECHO-9 virus was the interfering agent, which considerably suppressed the multiplication of poliovirus type 2, not only through a number of monkey kidney culture passages, but also in the CNS of monkeys. Since the high concentration of virus found in the CNS of the patient was mainly a result of a high concentration of the ECHO-9 component, the latter has apparently interfered with the poliovirus component also in the human CNS. A slight interfering effect of the poliovirus on the multiplication of ECHO-9 virus has been observed in suckling-mice. Although the ECHO-9 virus has entered the human CNS accompanied by poliovirus type 2, the neuroinvasiveness of the former, under certain conditions, is evident. Likewise, there is evidence of multiplication of this particular strain in the human and monkey CNS. The problem as to whether this virus is able to produce poliomyelitis-like lesions in the human CNS, however, remains to be solved.

The effect of sodium fluoride on responses to various central nervous system agents in rats

Rats given sodium fluoride at 10 mg/kg daily by the intraperitoneal route were more sensitive to the convulsant action of strychnine and pentylenetetrazol and to electroshock. This increase in sensitivity to CNS stimulation was observed also in two other groups of rats which were given a diet with added sodium fluoride amounting to 7 and 70 parts per million in terms of fluoride. Prolonged treatment with fluoride also lengthened the sleeping time induced by pentobarbital and increased the protective effect of diphenylhydantoin against electroshock. The increase in sensitivity to some CNS-active agents in the fluoride-treated rats disappeared after these rats were given the control diet for 2 weeks.

Electroencephalographic and behavioral effects of tofranil.

Intravenous administration of Tofrānil in 28 voluntary, open-ward psychiatric patients elicited electrographic patterns of desynchronization and an increase of theta rhythms, associated with behavioral alerting, relaxation and lassitude. Chronic administration of oral Tofrānil in 16 depressed and retarded psychiatric subjects elicited behavioral adaptations of euphoric denial in eight, restlessness and somatization in three and no change in five. During the fifth week of administration, electrographic desynchronization was manifest. It is concluded that Tofrānil is an active central nervous system agent, with a spectrum of activity most like experimental anticholinergic hallucinogens. The theoretic significance for neurophysiologic-behavioral constructs is briefly discussed.