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T Glaser

Publications and source records attributed to T Glaser.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sensitization to CD95 ligand-induced apoptosis in human glioma cells by hyperthermia involves enhanced cytochrome c release.

CD95L-induced apoptosis involves caspase activation and is facilitated when RNA and protein synthesis are inhibited. Here, we report that hyperthermia sensitizes malignant glioma cells to CD95L- and APO2L-induced apoptosis in the absence, but not in the presence, of inhibitors of RNA and protein synthesis. Hyperthermia does not alter CD95 expression at the cell surface and does not modulate the morphology of CD95-mediated cell death on electron microscopy. Bcl-2 gene transfer inhibits apoptosis and abrogates the sensitization mediated by hyperthermia. Hyperthermia does not overcome resistance to apoptosis conferred by the viral caspase inhibitor, crm-A, indicating the absolute requirement for the activation of crm-A-sensitive caspases, probably caspase 8, for apoptosis. CD95L-evoked DEVD-amc-cleaving caspase activity is enhanced by hyperthermia, suggesting that hyperthermia operates upstream of caspase processing to promote apoptosis. There is no uniformly enhanced processing of three caspase 3 substrates, poly-ADP ribose polymerase (PARP), protein kinase C (PKC) delta and DNA fragmentation factor (DFF) 45. Yet, hyperthermia promotes CD95L-evoked DNA fragmentation. Interestingly, hyperthermia enhances the CD95L-evoked release of cytochrome c in the absence, but not in the presence, of CHX. In contrast, the reduction of the mitochondrial membrane potential is enhanced by hyperthermia both in the absence and presence of CHX, and enhanced cytochrome c release is not associated with significantly enhanced caspase 9 processing. The potentiation of cytochrome c release at hyperthermic conditions in the absence of CHX is abrogated by Bcl-2. Thus, either hyperthermia or inhibition of protein synthesis by CHX potentiate cytotoxic cytokine-induced apoptosis. These pathways show no synergy, but rather redundance, indicating that CHX may function to promote apoptosis in response to cytotoxic cytokines by inhibiting the synthesis of specific proteins whose synthesis, function or degradation is temperature-sensitive.

Apoptosis↗
PubMed2000

Ligand K-edge X-ray absorption spectroscopy: a direct probe of ligand-metal covalency.

Ligand K-edge X-ray absorption spectroscopy (XAS) is a new experimental probe of the covalency of a metal-ligand bond. The intensity of the ligand pre-edge feature is proportional to the mixing of ligand orbitals into the metal d orbitals. The methodology to determine covalencies in one-electron (hole) and many-electron systems is described and demonstrated for a series of metal tetrachlorides [MCl(4)](n)(-), metal tetrathiolates [M(SR)(4)](n)(-), and dimeric iron-sulfur (Fe-S) clusters [Fe(2)S(2)(SR)(4)](2-). It is then applied to blue Cu proteins, the Cu(A) site, hydrogen bonding in Fe-S clusters, and the delocalization behavior in [2Fe-2S] vs [4Fe-4S] clusters. The covalencies determined in these studies provide important electronic structure insight into function.

Electron Probe Microanalysis↗
PubMed2000

Use of spoligotype analysis to detect laboratory cross-contamination.

Spoligotype analysis identified false-positive isolates of Mycobacterium tuberculosis caused by laboratory cross-contamination. Spoligotyping is faster, is less expensive than DNA fingerprinting, and can be used with a variety of media. Patients were reevaluated and had medications discontinued as a result of this investigation. Months of unnecessary patient follow-up and treatment were avoided.

Cross Infection↗
PubMed2000

Genomic, transcriptional and mutational analysis of the mouse microphthalmia locus.

Mouse microphthalmia transcription factor (Mitf) mutations affect the development of four cell types: melanocytes, mast cells, osteoclasts, and pigmented epithelial cells of the eye. The mutations are phenotypically diverse and can be arranged in an allelic series. In humans, MITF mutations cause Waardenburg syndrome type 2A (WS2A) and Tietz syndrome, autosomal dominant disorders resulting in deafness and hypopigmentation. Mitf mice thus represent an important model system for the study of human disease. Here we report the complete exon/intron structure of the mouse Mitf gene and show it to be similar to the human gene. We also found that the mouse gene is transcriptionally complex and is capable of generating at least 13 different Mitf isoforms. Some of these isoforms are missing important functional domains of the protein, suggesting that they might play an inhibitory role in Mitf function and signal transduction. In addition, we determined the molecular basis for six microphthalmia mutations. Two of the mutations are reported for the first time here (Mitf(mi-enu198) and Mitf(mi-x39)), while the others (Mitf(mi-ws), Mitf(mi-bws), Mitf(mi-ew), and Mitf(mi-di)) have been described but the molecular basis for the mutation not determined. When analyzed in terms of the genomic and transcriptional data presented here, it is apparent that these mutations result from RNA processing or transcriptional defects. Interestingly, three of the mutations (Mitf(mi-x39), Mitf(mi-bws), and Mitf(mi-ws)) produce proteins that are missing important functional domains of the protein identified in in vitro studies, further confirming a biological role for these domains in the whole animal.

Alleles↗
PubMed1999

Association of calpain (Ca(2+)-dependent thiol protease) with its endogenous inhibitor calpastatin in myoblasts.

Calpain isozymes (intracellular, Ca(2+)-dependent thiol proteases) are present in the cytoplasm of many cells, along with their endogenous specific inhibitor, calpastatin. Previously, we found that the levels of mu-calpain and m-calpain (activated by microM and mM Ca(2+), respectively) remain about the same during myoblast differentiation and fusion. By contrast, the calpastatin level, which is high during the initial stages of differentiation, diminishes markedly before myoblast fusion, allowing the proteolysis that is required for myotube formation. In the present study, we used immunoprecipitation to investigate the molecular association between calpain and calpastatin in dividing myoblasts and in the initial stages of myoblast differentiation. Immunoprecipitation (IP) was performed in two ways: (1) IP of calpain, using an anti-calpain antibody that recognized both isozymes; and (2) IP of calpastatin (using anti-calpastatin). Calpastatin was co-precipitated when calpain was immunoprecipitated; calpain was co-precipitated when calpastatin was immunoprecipitated. The results indicate that calpastatin is associated with calpain in dividing myoblasts and in myoblasts during the initial stages of differentiation, thereby preventing calpain activation at this stage. Prior studies carried out in vitro have shown a Ca(2+)-dependent interaction of calpain with calpastatin. The results described here suggest that an association between calpain and calpastatin could occur within cells in the presence of physiological Ca(2+)levels. It is proposed that the status of cellular calpain-calpastatin association is modulated by cell constituents, for which some possibilities are suggested.

Animals↗
PubMed1999

Death ligand/receptor-independent caspase activation mediates drug-induced cytotoxic cell death in human malignant glioma cells.

Death ligand/receptor interactions and caspase activation mediate drug-induced apoptosis in certain cancer cells. The molecular mechanisms responsible for the chemoresistance of human malignant gliomas are largely unknown. Here, we report that malignant glioma cells co-express CD95 and CD95L without undergoing suicidal or fratricidal apoptosis. Glioma cells do not commit CD95/CD95L-dependent suicide or fratricide even when RNA and protein synthesis are inhibited. This is because ectopic expression of the viral caspase inhibitor, crm-A, or exposure to a neutralizing CD95L antibody, block apoptosis induced by exogenous CD95L but not cell death induced by cytotoxic concentrations of inhibitors of RNA and protein synthesis. Although some cytotoxic drugs enhance the expression of CD95 or CD95L, crm-A fails to block drug-induced cytotoxic and clonogenic cell death, suggesting that the drug-induced changes in CD95 and CD95L expression are epiphenomenal. There is also no difference in drug-induced apoptosis between crm-A-transfected and control cells as assessed by electron microscopy, in situ DNA end labeling and DNA fragmentation. Further, glioma cells selected for resistance to CD95L do not acquire cross-resistance to chemotherapy. However, the broad spectrum caspase inhibitor, ZVAD-fmk, inhibits drug-induced cytotoxic cell death, suggesting a role of crm-A-insensitive caspases in drug-induced apoptosis of glioma cells. Thus, drug resistance of malignant glioma cells may involve deficiencies in two interrelated pathways that mediate death in order tumor cell types: (i) death ligand/receptor signalling; and (ii) caspase activation.

Antineoplastic Agents↗
PubMed1999

Boswellic acids and malignant glioma: induction of apoptosis but no modulation of drug sensitivity.

Steroids are essential for the control of oedema in human malignant glioma patients but may interfere with the efficacy of chemotherapy. Boswellic acids are phytotherapeutic anti-inflammatory agents that may be alternative drugs to corticosteroids in the treatment of cerebral oedema. Here, we report that boswellic acids are cytotoxic to malignant glioma cells at low micromolar concentrations. In-situ DNA end labelling and electron microscopy reveal that boswellic acids induce apoptosis. Boswellic acid-induced apoptosis requires protein, but not RNA synthesis, and is neither associated with free radical formation nor blocked by free radical scavengers. The levels of BAX and BCL-2 proteins remain unaltered during boswellic acid-induced apoptosis. p21 expression is induced by boswellic acids via a p53-independent pathway. Ectopic expression of wild-type p53 also induces p21, and facilitates boswellic acid-induced apoptosis. However, targeted disruption of the p21 genes in colon carcinoma cells enhances rather than decreases boswellic acid toxicity. Ectopic expression of neither BCL-2 nor the caspase inhibitor, CRM-A, is protective. In contrast to steroids, subtoxic concentrations of boswellic acids do not interfere with cancer drug toxicity of glioma cells in acute cytotoxicity or clonogenic cell death assays. Also, in contrast to steroids, boswellic acids synergize with the cytotoxic cytokine, CD95 ligand, in inducing glioma cell apoptosis. This effect is probably mediated by inhibition of RNA synthesis and is not associated with changes of CD95 expression at the cell surface. Further studies in laboratory animals and in human patients are required to determine whether boswellic acids may be a useful adjunct to the medical management of human malignant glioma.

Animals↗
PubMed1999

Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma.

The inhibitor-of-apoptosis (IAP) proteins are a novel family of antiapoptotic proteins that are thought to inhibit cell death via direct inhibition of caspases. Here, we report that human malignant glioma cell lines express XIAP, HIAP-1 and HIAP-2 mRNA and proteins. NAIP was not expressed. IAP proteins were not cleaved during CD95 ligand (CD95L)-induced apoptosis, and loss of IAP protein expression was not responsible for the potentiation of CD95L-induced apoptosis when protein synthesis was inhibited. LN-18 cells are highly sensitive to CD95-mediated apoptosis, whereas LN-229 cells require co-exposure to CD95L and a protein synthesis inhibitor, CHX, to acquire sensitivity to apoptosis. Adenoviral XIAP gene transfer blocked caspase 8 and 3 processing in both cell lines in the absence of CHX. Apoptosis was blocked in the absence and in the presence of CHX. However, XIAP failed to block caspase 8 processing in LN-229 cells in the presence of CHX. There was considerable overlap of the effects of XIAP on caspase processing with those of BCL-2 and the viral caspase inhibitor crm-A. These data define complex regulatory mechanisms for CD95-mediated apoptosis in glioma cells and indicate that there may be a distinct pathway of death receptor-mediated apoptosis that is readily activated when protein synthesis is inhibited. The constitutive expression of natural caspase inhibitors may play a role in the resistance of these cells to apoptotic stimuli that directly target caspases, including radiochemotherapy and immune-mediated tumor cell lysis.

Adenoviridae↗
PubMed1999

[Direct and indirect costs of schizophrenia].

In the present study the costs of schizophrenia in Germany were studied using the "bottom up" prevalence-based method. In a random sample of 180 schizophrenic patients stratified according to the most important care institutions, direct and indirect costs were retrospectively documented for a 12-month period. Depending on the place of recruitment and the extent of care provided, total yearly costs result between about DM 33,000 for a patient treated predominantly on an outpatient basis and about DM 126,000 for a patient requiring hospital care and about DM 135,000 for a patient in job rehabilitation. The direct yearly treatment costs were, as expected, lowest for patients recruited in the private practice of a psychiatrist and predominantly treated on an outpatient basis (DM 5,788), and were the highest in the psychiatric hospital (DM 64,661) and in job rehabilitation (DM 79,996). In the patients recruited in the outpatient domain, doctors' fees and medication together were responsible for only 4.5% of the total costs, whereas the indirect costs (e.g., through work incapacity) were responsible for 87% of the total yearly costs. For methodological reasons the total costs caused by schizophrenic psychoses in Germany per year can at present be estimated only roughly. A conservative estimate is between 8.5 and 18 billion DM per year. The study shows that schizophrenia is a very expensive illness, the direct and indirect costs of which are on the whole comparable to those of the common somatic illnesses. Therefore, also for economical reasons, sufficient financial means should be invested in the research and treatment of this severe illness.

Adult↗
PubMed1998

APO2 ligand: a novel lethal weapon against malignant glioma?

APO2L (TRAIL) is a novel CD95L (Fas/APO-1-L) homologous cytotoxic cytokine that interacts with various receptors which transmit (DR4, DR5) or inhibit (DcR1, DcR2) an apoptotic signal. Here, we report that human glioma cell lines preferentially express mRNAs for agonistic death receptors DR4 (8/12) and DR5 (11/12) rather than the death-inhibitory decoy receptors DcR1 (4/12) and DcR2 (2/12). Ten of 12 cell lines are susceptible to APO2L-induced apoptosis. The resistant cell lines, U138MG and U373MG, are cross-resistant to CD95L-induced apoptosis. Similar to CD95L-induced apoptosis, APO2L-induced apoptosis is inhibited by ectopic expression of the caspase inhibitor, crm-A, or of bcl-2, or by coexposure to the corticosteroid, dexamethasone, or the lipoxygenase inhibitor, nordihydroguaretic acid. There is no correlation between p53 genetic status of the cell lines and their susceptibility to APO2L-induced apoptosis, but the latter is moderately enhanced by ectopic expression of wild-type p53. APO2L targeting may be a promising approach for selectively targeting apoptosis to human malignant glioma cells.

Apoptosis↗
PubMed1998

The calpain-calpastatin system and protein degradation in fusing myoblasts.

Calpain (Ca(2+)-activated cysteine protease) induced proteolysis has been suggested to play a role in myoblast fusion. We previously found that calpastatin (the endogenous inhibitor of calpain) diminishes markedly in myoblasts during myoblast differentiation just prior to the start of fusion, allowing Ca(2+)-induced calpain activation at that stage. Here, we show that a limited degradation of some proteins occurs within the myoblasts undergoing fusion, but not in proliferating myoblasts. The protein degradation is observed at the stage when calpastatin is low. Protein degradation within the myoblasts and myoblast fusion are inhibited by EGTA, by the cysteine protease inhibitors calpeptin and E-64d and by calpastatin. The degradation appears to be selective for certain myoblast proteins. Integrin beta 1 subunit, talin and beta-tropomyosin are degraded in the fusing myoblasts, whereas alpha-actinin, beta-tubulin and alpha-tropomyosin are not. A similar pattern of degradation is observed in lysates of proliferating myoblasts when Ca2+ and excess calpain are added, a degradation that is inhibited by calpastatin. The results support the notion that degradation of certain proteins is required for myoblast fusion and that calpain participates in the fusion-associated protein degradation. Participation of calpain is made possible by a change in calpain/calpastatin ratio, i.e., by a diminution in calpastatin level from a high level in the proliferating myoblasts to a low level in the differentiating myoblasts. Degradation of certain proteins, known to be responsible for the stability of the membrane-skeleton organization and for the interaction of the cell with the extracellular matrix, would allow destabilization of the membrane and the creation of membrane fusion-potent regions.

Animals↗
PubMed1998

cDNA cloning, recombinant expression and characterization of polypetides with exceptional DNA affinity.

Polypeptides remaining tightly associated with isolated genomic DNA are of interest with respect to their potential involvement in the topological organization and/or function of genomic DNA. Such residual DNA-polypeptide complexes were used for raising monoclonal antibodies by in vitro immunization. Screening of a murine lambdagt11 cDNA library with these antibodies released a positive cDNA (MC1D) encoding a 16 kDa polypeptide. The cloned homologous human cDNA (HC1D) was identified in the dbest data base by partial sequence comparison, and it was sequenced full length. The cDNA-derived amino acid sequences comprise nuclear location signals but none of the known DNA-binding motifs. However, the recombinantly expressed proteins show in vitro DNA binding affinities. A polyclonal antiserum to the recombinant MC1D protein immunostains sub-nuclear structures, and it detects a residual 16 kDa polypeptide on western blots of DNA digests. These results support the conclusion that the cloned cDNAs reflect mRNAs encoding one of the chemically-resistant polypeptides which can be detected in isolated genomic DNA by sensitive techniques, e.g. by125Iodine labeling and SDS-PAGE.

Amino Acid Sequence↗
PubMed1998

Upregulation of the calcium-dependent protease, calpain, during keratinocyte differentiation.

Calpain is a ubiquitous neutral calcium-activated thiol protease that is implicated in various cellular functions including exocytosis, cell fusion, apoptosis and proliferation. The calpain system is composed of the enzymes mu-calpain and m-calpain and their endogenous inhibitor, calpastatin. We employed the spontaneously immortalized human HaCaT keratinocytes, which retain their ability to differentiate in vitro and in vivo, to study the modulation of the calpain system during keratinocyte differentiation. The cellular levels of keratinocyte differentiation markers and of the components of the calpain system were monitored by immunoblotting. Three established differentiation stimuli: increase in cell density as a function of time in culture, elevation of extracellular calcium concentration and exposure to 1,25-dihydroxyvitamin D3 enhanced the expression of the three keratinocyte differentiation markers keratin 10, involucrin and transglutaminase. The differentiation of HaCaT cells was accompanied by elevation of the components of the calpain system, although the pattern of increase varied according to the specific differentiation stimulus. A higher increase in calpains as compared with the increase in calpastatin suggests an increase in net calpain activity during differentiation. Such an increase may play a part in the differentiation process itself and/or in the regulation of key events in differentiating keratinocyte metabolism.

Calpain↗
PubMed1998

[Positive and negative symptoms in chronic schizophrenic patients under maintenance therapy with flupenthixol decanoate for a twelve month perioid].

62 chronic schizophrenics, who after a psychotic exacerbation were stabilized again, were randomized on 3 different maintenance dosages of flupentixol-decanoate and observed for 12 months. 15 (24.2%) patients had a relapse independently of the dose. 34 of the 47 patients without relapse had complete documentations of the follow-up. After 3 to 6 months there was an obvious and constant clinical improvement as assessed by various test inventories. The BPRS-scores for psychopathology, negative and positive symptoms improved significantly between 14 to 18%. There was also significant reduction of negative symptoms assessed by SANS (22%) as well in the severity of illness (CGI) and an amelioration of psychosocial functioning (GAS, Strauss-Carpenter). At the end of trial 26.4% of the patients had mild involuntary movements (AIMS), 23.5% were on antiparkinson-medication. It is concluded that there could be an indication for flupentixol-decanoate in the long term maintenance therapy especially of chronic schizophrenics with negative symptoms and problems of compliance under oral medication.

Adult↗
PubMed1998

Mutation at the anophthalmic white locus in Syrian hamsters: haploinsufficiency in the Mitf gene mimics human Waardenburg syndrome type 2.

Mutations in MITF (microphthalmia transcription factor) cause Waardenburg syndrome type 2 (WS2A) in humans, an autosomal dominant disorder consisting of deafness and hypopigmentation. Phenotypes vary significantly within WS2 pedigrees, and there is generally no correlation between the predicted biochemical properties of mutant MITF proteins and disease severity. We have identified a nonsense mutation in the Mitf gene of the anophthalmic white Wh) Syrian hamster that destabilizes its mRNA and prevents the encoded basic helix-loop-helix leucine zipper (bHLHzip) protein from dimerizing or binding DNA target sites. Although the resulting polypeptide does not act as a dominant-negative species in vitro , the Wh mutation is inherited as a semi-dominant trait. It thus more closely resembles WS2 than comparable Mitf alleles in laboratory mice and rats, which are expressed as purely recessive traits.

Amino Acid Sequence↗
PubMed1998

Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis.

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.

Amino Acid Sequence↗
PubMed1998

Characterization of the aminomethylchroman derivative BAY x 3702 as a highly potent 5-hydroxytryptamine1A receptor agonist.

The aminomethylchroman derivative BAY x 3702 (R-(-)-2-[4-[(chroman-2-ylmethyl)-amino]-butyl]-1,1-dioxo-benzo[d] isothiazolone hydrochloride) is a new high affinity 5-hydroxytryptamine (5-HT)1A receptor ligand [calf hippocampus: Ki: 0.19 nM; reference compounds 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and ipsapirone: 0.98 and 2.56, respectively; rat cortex: 0.24 nM; rat hippocampus: 0.58 nM; human cortex and recombinant 5-HT1A receptors: 0.25 and 0.4 nM, respectively]. BAY x 3702 bound also with relatively high to moderate affinity to the following receptors: alpha-1 and alpha-2 adrenergic (Ki: 6 and 7 nM, respectively); 5-HT7- and 5-HT1D (7 and 36 nM); dopamine D2- and D4 (48 and 91 nM); sigma sites (176 nM) and 5-HT2C (310 nM); others: > 10 microM, as obtained in more than 50 different binding assays. In the forskolin-stimulated adenylate cyclase assay in rat hippocampal tissue, a model of postsynaptic 5-HT1A receptor function, BAY x 3702 was a potent 5-HT1A receptor full agonist (IC50: 1.9 nM; 8-OH-DPAT: 25.3 nM, full agonist; ipsapirone: partial agonist) and its effects could be completely blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide trihydrochloride (WAY-100635). At those receptors where BAY x 3702 bound with lower affinity, the compound appeared to be either an agonist (5-HT1D receptors) or an antagonist (alpha-1, alpha-2 and D2 receptors). In a rat brain slice preparation containing the dorsal raphe nucleus (DRN), a model of somatodendritic 5-HT1A receptor function, BAY x 3702 inhibited potently (1 nM) neuronal firing. Also in vivo, BAY x 3702 (0.5 microgram/kg, i.v.) was found to suppress 5-HT neuronal firing in the DRN of anesthetized rats. In both electrophysiological assays BAY x 3702 was more potent than 8-OH-DPAT and ipsapirone; the potency difference being about 1 and 2 orders of magnitude, respectively. In rats trained to discriminate 8-OH-DPAT (0.1 mg/kg, i.p.) in a drug discrimination procedure, complete generalization was obtained with BAY x 3702 (ED50: 0.022 mg/kg, i.p. and 0.38 mg/kg, p.o.; 8-OH-DPAT: 0.028 mg/kg, i.p. and ipsapirone: 0.44 mg/kg, i.p.). In the rat hypothermia model BAY x 3702 induced a WAY-100635-reversible effect and the compound had a higher potency and intrinsic activity than 8-OH-DPAT and ipsapirone (ED50: 0.25 mg/kg, i.p. and 5.4 mg/kg, p.o., respectively; 8-OH-DPAT: 1.1 mg/kg, i.p. and ipsapirone: 6.2 mg/kg, i.p.). BAY x 3702 induced a stimulation of plasma ACTH levels in the rat; the effect being again more pronounced than that of ipsapirone (ED50: 7.5 and 25.3 mg/kg, p.o., respectively). It is concluded that BAY x 3702 is a relatively selective 5-HT1A receptor agonist with high potency and intrinsic activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗