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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Tetrahedron 24 (1968), S. 619-624 
    ISSN: 0040-4020
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Tetrahedron 26 (1970), S. 5789-5791 
    ISSN: 0040-4020
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Graefe's archive for clinical and experimental ophthalmology 158 (1956), S. 197-227 
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 276-282 
    ISSN: 1432-1912
    Keywords: Key words BIMT 17 ; Receptor binding ; 5-HT1A receptor ; 5-HT2A receptor ; Adenylyl cyclase (forskolin-stimulated) ; Pl turnover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the search for antidepressant agents with a rapid onset of action, we have found that compound BIMT 17 (1-[2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethyl]benzimidazol-[1H]-2-one) shows a good affinity for cerebral cortical 5-HTIA (pK i=7.72) and 5-HT2A (pK i=6.90) receptors, with no appreciable affinity for the other 5-HT receptor subtypes, including 5-HT2C. BIMT 17 reduced forskolin-stimulated cAMP accumulation in the cerebral cortex (pEC50=6.09) and in the hippocampus (pEC50=6.50), and antagonized 5-HT-induced phosphatidylinositol turnover (pK i=6.96) in the cerebral cortex. The effect on cAMP accumulation was blocked by the 5-HT1A receptor antagonist tertatolol. Buspirone, 8-OH-DPAT and S 14671 {1-[2-(2-thenoylamino)ethyl]-4[1-(7-methoxynaphtyl)]-piperazine}, claimed to be 5-HT1A receptor agonists, did not reduce forskolin-stimulated cAMP formation in the cerebral cortex. On the basis of these data, it was concluded that BIMT 17 was the only compound that behaved as a full agonist with respect to the cAMP response in the cortex, while exerting concurrent agonism at 5-HT1A receptors and antagonism at 5-HT2A receptors. These characteristics might explain the peculiar behaviour of BIMT 17 in mimicking the inhibitory action of 5-HT on the basal firing rate of the cortical neurons (see accompanying paper).
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1912
    Keywords: BIMT 17 ; 5-HT1A receptors ; 5-HT2A receptors ; Extracellular recording
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract BIMT 17 (1-[2-[4-(3-trifluoromethyl phenyl) piperazin-1-yl] ethyl] benzimidazol- [1H]-2-one), a 5-HT1A receptor agonist/5-HT2A receptor antagonist (see Borsini et al., accompanying paper), in a dose range of 1–10 mg/kg i.v., dose-dependently inhibited the electrical activity of rat medial prefronto-cortical neurons, whereas buspirone, in a dose range of 0.1–1000 μg/kg, increased it. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 1-[2-(2-thenoylamino)ethyl]-4[1-(7-methoxynaphthyl)] piperazine (S 14671) presented biphasic patterns of response; they increased electrical activity at doses in the range of 0.1–10 μg/kg and 0.1–3 μg/kg i.v. respectively, and reduced it at higher doses, 30–300 μg/kg and 10–30 μg/kg i.v., respectively. The inhibitory effect of BIMT 17 on the firing rate of neurons in the frontal cortex was antagonized by the 5-HT1A antagonists tertatolol and WAY 100135, and was still present after destruction of serotonin (5-HT) containing neuronal endings by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 150 μg/rat, given intraventricularly), which reduced the cortical 5-HT content by 85%. This destruction of 5-HT neurons, while suppressing the ability of 8-OH-DPAT to inhibit the firing rate at high doses, did not change the excitatory action of this compound at low doses. The addition of ritanserin, a 5-HT2A receptor antagonist, potentiated both the excitatory and inhibitory effects of 8-OHDPAT on neuronal electrical activity. Direct microiontophoretic application (100 nA/20 s) of 5-HT and BIMT 17, but not that of 8-OH-DPAT, onto medial prefronto-cortical neurons, decreased the firing rate of these neurons. These findings suggest that BIMT 17 directly inhibits the electrical activity of medial prefronto-cortical neurons through its dual mode of receptor interaction.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1912
    Keywords: Key words BIMT 17 ; 5-HT1A receptors ; 5-HT2A receptors ; Extracellular recording
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  BIMT 17 (1- [2- [4-(3-trifluoromethyl phenyl) piperazin-1-yl] ethyl] benzimidazol- [1H]-2-one), a 5-HT1A receptor agonist/5-HT2A receptor antagonist (see Borsini et al., accompanying paper), in a dose range of 1–10 mg/kg i.v., dose-dependently inhibited the electrical activity of rat medial prefronto-cortical neurons, whereas buspirone, in a dose range of 0.1–1000 μg/kg, increased it. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 1-[2-(2-thenoylamino)ethyl]-4-[1-(7-methoxynaphthyl)] piperazine (S 14671) presented biphasic patterns of response; they increased electrical activity at doses in the range of 0.1–10 μg/kg and 0.1–3 μg/kg i.v. respectively, and reduced it at higher doses, 30–300 μg/kg and 10–30 μg/kg i.v., respectively. The inhibitory effect of BIMT 17 on the firing rate of neurons in the frontal cortex was antagonized by the 5-HT1A antagonists tertatolol and WAY 100135, and was still present after destruction of serotonin (5-HT) containing neuronal endings by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 150 μg/rat, given intraventricularly), which reduced the cortical 5-HT content by 85%. This destruction of 5-HT neurons, while suppressing the ability of 8-OH-DPAT to inhibit the firing rate at high doses, did not change the excitatory action of this compound at low doses. The addition of ritanserin, a 5-HT2A receptor antagonist, potentiated both the excitatory and inhibitory effects of 8-OH-DPAT on neuronal electrical activity. Direct microiontophoretic application (100 nA/20 s) of 5-HT and BIMT 17, but not that of 8-OH-DPAT, onto medial prefronto-cortical neurons, decreased the firing rate of these neurons. These findings suggest that BIMT 17 directly inhibits the electrical activity of medial prefronto-cortical neurons through its dual mode of receptor interaction.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 276-282 
    ISSN: 1432-1912
    Keywords: BIMT 17 ; Receptor binding ; 5-HT1A receptor ; 5-HT2A receptor ; Adenylyl cyclase (forskolin-stimulated) ; Pl turnover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the search for antidepressant agents with a rapid onset of action, we have found that compound BIMT 17 (1-[2-[4-(3-trifluoromethylphenyl)piperazin1-yl]ethyl]benzimidazol-[1H]-2-one) shows a good affinity for cerebral cortical 5-HT1A (pK i = 7.72) and 5-HT2A (pK i = 6.90) receptors, with no appreciable affinity for the other 5-HT receptor subtypes, including 5-HT2C. BIMT 17 reduced forskolin-stimulated cAMP accumulation in the cerebral cortex (pEC50 = 6.09) and in the hippocampus (pEC50 = 6.50), and antagonized 5-HT-induced phosphatidylinositol turnover (pK i = 6.96) in the cerebral cortex. The effect on cAMP accumulation was blocked by the 5-HT1A receptor antagonist tertatolol. Buspirone, 8-OH-DPAT and S 14671 {1-[2-(2-thenoylamino)ethyl]-4[1-(7-methoxynaphtyl)]piperazine, claimed to be 5-HT1A receptor agonists, did not reduce forskolin-stimulated cAMP formation in the cerebral cortex. On the basis of these data, it was concluded that BIMT 17 was the only compound that behaved as a full agonist with respect to the CAMP response in the cortex, while exerting concurrent agonism at 5-HT1A receptors and antagonism at 5-HT2A receptors. These characteristics might explain the peculiar behaviour of BIMT 17 in mimicking the inhibitory action of 5-HT on the basal firing rate of the cortical neurons (see accompanying paper).
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 35 (1957), S. 261-263 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been hypothesized that bidentate hydrogen bonding plays an important role in the interaction of imidazolylphenylformamidines with the H2-receptor. The present study, in which the degree of pseudoirreversible H2-antagonism of the four isomeric butyl substituted mifentidine analogues was determined on the spontaneously beating right atrium of the male guinea-pig, lends further support to this hypothesis. In solution the EE/EZ ratio is different for the four isomeric butylated mifentidine analogues. The rank order of the percentage of E,E conformation, which favors a bidentate interaction, of the formamidine moiety parallels the rank order of pseudo-irreversible H2-antagonism.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Documenta ophthalmologica 14 (1960), S. 135-165 
    ISSN: 1573-2622
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'Auteur passe en revue les apports les plus récents au sujet de l'étiologie virale des uvéites. On souligne avant tout le double aspect de la question: d'un coté, possibilités pathogènes mises en évidence expérimentalement chez des virus connus; d'un autre coté, apparition d'uvéites spontanées attribuables à une étiologie virale. On souligne le fait que les uvéites virales (d'habitude antérieures, légères, et d'évolution bénigne) sont constatées cliniquement surtout au cours d'une affection virale plus ou moins généralisée, et beaucoup moins fréquemment comme manifestation monosymptomatique. La mise en évidence d'une cause virale des uvéites est rendue particulièrement difficile par diverses éventualités, et surtout par la possibilité de fixation sur l'uvée d'autres agents - virus ou bactéries - au cours de la maladie virale. On peut encore rencontrer des processus uvéaux de nature plutôt toxique ou allergique, que strictement viraux. Parmi les virus reconnus responsables d'uvéites plus ou moins monosymptomatiques, on rappelle essentiellement ceux de l'herpès simplex et de l'herpès zoster (avec ou sans participation cornéenne). On a encore relevé d'autres uvéites au cours de la varicelle, de la grippe, de la mononucléose infectieuse, de la variole et de la vaccine, de la parotidite épidémique, de la rougeole, de la dengue, de l'hépatite épidémique, de la fièvre de la Vallée du Rift, de la maladie à inclusions cytomégaliques, et enfin du lymphogranulome vénérien. Dans ce dernier cas la Symptomatologie générale peut être nulle ou très légère L'attribution d'uvéites au virus de la kératoconjonctivité épidémique et surtout à celles de la verrue vulgaire et du trachome est discutable. L'importance des virus de la maladie de Newcastle, de l'ornithose, de la pseudo-rabies, et de certains virus encéphalitiques pour la genèse des uvéites est purement expérimentale. L'Auteur conclut en rappelant qu'on a supposé une origine virale même pour un groupe d'autres affections dans lesquelles l'uvéite est un des signes parfois le plus important. Il s'agit des uvéo-méningites (syndromes de Harada, de Vogt-Koyanagi, de l'ophtalmie sympathique) et des syndromes muco-cutanéo-oculaires (syndromes de Reiter, de Behçet et de Stevens-Johnson). On a retrouvé des uvéites également dans certaines réticuloendothélioses et dans la sclérose en plaques, pour lesquelles l'hypothèse d'une étiologie virale a été émise. La nature virale des syndromes énumérés ci-dessus n'est pas encore cependant généralement admise. L'importance des virus dans l'étiologie des uvéites s'étendrait si l'on pouvait établir un rôle éventuel des adénovirus, des coxsackies et des virus ECHO dans la détermination des inflammations uvéales.
    Abstract: Summary The author gives a review of the most recent publications on the viral aetiology of uveitis. He emphasizes the double aspect of the question: on one hand establishment of the pathogenesis by the experimental proof of viruses already kown, on the other hand spontaneous types of uveitis, which can be attributed to viral etiology. Clinically the cases of uveitis caused by virus (mostly mild and benign diseases of the anterior segment) usually appear during the course of a more or less generalized viral disease and only seldom are monosymptomatic. To establish the value of a virus as morbific agent is especially difficult because of different reasons. In the course of a viral disease also other causative agents (bacteria or other viruses) affect the uvea, moreover there are uveal findings, which are more of a toxic or allergic nature than of a pure viral one. As causative agents of uveitis preponderantly the virus of herpes simplex and herpes zoster (with or without participation of the cornea) are to be incriminated. Furthermore uveitis has been observed in the course of varicella, influenza, infectious mononucleosis, variola, cow-pox, epidemic parotitis, measles, dengue, epidemic hepatitis, Rift Valley fever, cytomegalic inclusion disease, and finally venereal lymphogranuloma. In the last case sometimes no or only slight general symptoms may be observed. The viral etiology of uveitis in connection with epidemic keratoconjunctivitis, verruca vulgaris, and trachoma is controversial. The viruses of Newcastle disease, ornithosis, pseudo-rabies, and some virus of encephalitis are of only experimental importance as to the origin of uveitis. The author calls attention to the fact that eventually a viral aetiology has been assumed even in a group of diseases, where the uveitis is only a symptom, sometimes the most important. That is the case where uveitis and meningitis are combined (Syndrome of Harada and Vogt-Koyanagi, sympathethic ophthalmia) or in syndromes with affection of mucous membranes, skin, and eyes (Reiter's syndrome, Behçet's syndrome, Stevens-Johnson-syndrome). Moreover the hypothesis of a viral etiology has been advanced for uveitis in certain reticulo-endothelioses and in multiple sclerosis. It is not generally accepted, however, that the syndromes mentioned here are being caused by infectious agents of the virus group. The importance of viruses for the etiology of uveitis would increase, if the possible rôle of adenoviruses, coxackies, and ECHO viruses in inflammatory uveal processes could be established.
    Notes: Riassunto L'Autore passa in rassegna i più recenti contributi in materia di etiologia virale delle uveiti. Viene anzitutto sottolineato il duplice aspetto della questione, rappresentato da un lato dalle capacità patogene esplicate sperimentalmente da parte di virus noti e dall'altro dalla comparsa di uveiti spontanee, riferibili ad un'etiologia virale. Viene sottolineato come uveiti virali (di solito anteriori, lievi o ad evoluzione benigna) siano state clinicamente constatate sopratutto nel corso di un'affezione da virus più o meno generalizzata, in modo assai meno frequente come manifestazione monosintomatica. Il riconoscimento di una causa virale delle uveiti è reso particolarmente difficile da varie eventualità e sopratutto dalla possibilità che nel corso della malattia virale altri agenti, virus o batteri, si possano fissare nell' uvea, nonchè che si verifichino processi uveali di natura tossica o allergica, anzichè strettamente virali. Fra i virus riconosciuti responsabili di uveiti più o meno monosintomatiche vengono essenzialmente ricordati quelli dell'herpes simplex e dell'herpes zoster (con e senza partecipazione corneale). Altre uveiti sono state poi rilevate nel corso di una varicella, dell'influenza, della mononucleosi infettiva, del vaiolo e di infezioni vacciniche, della parotite epidemica, del morbillo, della dengue, dell'epatite epidemica, della febbre della valle di Rift, delle malattie ad inclusioni citomegaliche ed infine nel linfogranuloma venereo. In quest' ultimo anche la sintomatologia generale è poco o nulla apparente. Discutibile appare l'attribuzione di uveiti al virus della cheratocongiuntivite epidemica e sopratutto a quelli della verruca volgare e del tracoma. Il valore dei virus della malattia di Newcastle, dell'ornitosi, della pseudorabies e di certi virus encefalitici per la genesi di uveiti è puramente sperimentale. L'Autore conclude col ricordare che un'etiologia virale è stata supposta anche per un gruppo di affezioni nelle quali l'uveite è uno dei segni talvolta principali. Si tratta delle cosidette uveo-meningiti (sindrome di Harada, di Vogt-Koyanagi, dell'oftalmia simpatica) e delle sindromi muco-cutanee-oculari (sindromi di Reiter, di Behçet e di Stevens-Johnson). Anche in certe reticolo-endoteliosi e nella sclerosi in placche, per le quali è stata avanzata un'ipotesi etiologica virale, si constatano uveiti. La natura virale delle sindromi su ricordate non trova però ancora il generale consenso. L'importanza dei virus nell'etiologia delle uveiti si estenderebbe qualora si potesse stabilire un eventuale valore degli adenovirus, dei coxsackie e dei virus ECHO nel determinare le flogosi uveali.
    Type of Medium: Electronic Resource
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