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J Lehmann

Publications and source records attributed to J Lehmann.

At least 37 records · Page 2Linked to original sources
PubMed2004

The strong inhibition of triosephosphate isomerase by the natural beta-carbolines may explain their neurotoxic actions.

The natural beta-carbolines (BC) closely resemble the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in structure. The N-methylated beta-carbolinium ions (BC+) are potent inhibitors of mitochondrial respiration and are nigrostriatal neurotoxins. Utilizing [3H]BC, we have identified several proteins to which BC binds with high affinity (e.g. the chaperone member glucose regulated protein 78, the enzyme carboxylesterase, the cytochrome P450 2E1, the enzyme monoamine oxidase B and a small G-protein of the Rho subfamily). In the present study we isolated a protein from bovine brain to which [3H]BC binds with high affinity and identified it being the enzyme triosephosphate isomerase (TPI; EC 5.3.1.1.). 2,9-Dimethyl-BC+ was the most potent inhibitor of TPI, clearly more potent than the known inhibitors. TPI deficiency is a rare disorder in humans characterized by a severe progressive extrapyramidal course. Thus, TPI inhibition could contribute to neurodegeneration observed after injection of BCs into substantia nigra. Furthermore, the findings fit into the hypothesis of BCs as endogenous toxins responsible for neurodegeneration.

Animals↗
PubMed2004

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

Adrenal Gland Neoplasms↗
PubMed2003

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany].

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

Adult↗
PubMed2003

Mucin 7 and cytokeratin 20 as new diagnostic urinary markers for bladder tumor.

PURPOSE: We determine the sensitivity and specificity of cytokeratin 20 (CK-20) and mucin 7 (MUC7) gene expression in voided urine samples taken from patients with bladder tumor and from control groups to investigate putative, noninvasive urinary markers for bladder tumor detection and monitoring. MATERIALS AND METHODS: Voided urine samples were collected from 50 patients with histologically proven bladder neoplasms (pTaN0M0G1-3 in 19 and pTisN0M0G3-pT4pN1M1G3 in 31), 20 patients with urolithiasis, 20 patients with urinary tract infection, 20 patients with other urological neoplasms and 20 healthy volunteers. Total RNA was extracted from exfoliated cells collected from 200 ml. voided urine. All RNA samples were investigated by a specific CK-20 and MUC7 nested reverse transcriptase polymerase chain reaction. RESULTS: The overall sensitivity of CK-20 gene expression in voided urine samples for the detection of bladder neoplasms was 78%. In contrast, voided urine samples from control patients and healthy volunteers showed a high rate of false-positive CK-20 detection resulting in a low specificity of 36%. The overall sensitivity of the MUC7 test for all bladder tumor cases was 66%. The sensitivity for papillary urothelial neoplasms (pTaN0M0G1-3) was 42% whereas analysis of the carcinoma in situ and invasive bladder cancer group (pTisN0M0G3-pT4pN1M1G3) yielded a sensitivity of 81%. The overall specificity of the MUC7 nested reverse transcriptase polymerase chain reaction method in the control groups was 80%. CONCLUSIONS: A high positive CK-20 detection rate was found not only in voided urine samples from patients with bladder tumor, but also in urine specimens from control groups. Therefore, CK-20 is not a reliable urinary tumor marker for bladder neoplasms. In contrast to CK-20, analysis of MUC7 demonstrated a high sensitivity and high specificity for carcinoma in situ and invasive bladder cancer, thus fulfilling the criteria of a urinary tumor marker.

Adult↗
PubMed2003

Improved risk-benefit ratio for topical triamcinolone acetonide in Transfersome in comparison with equipotent cream and ointment: a randomized controlled trial.

BACKGROUND: Transfersome is a drug delivery technology based on highly deformable, ultraflexible lipid vesicles which penetrate the skin when applied non-occlusively. OBJECTIVES: To assess the advantages of this carrier-based formulation in humans, the efficacy and the atrophogenic potential of triamcinolone acetonide (TAC) in Transfersome was compared with commercially available TAC-containing cream and ointment. METHODS: Healthy volunteers were enrolled in double-blind, placebo-controlled clinical trials with random study medication assignment to the test areas. RESULTS: A 10-fold lower dose of TAC in Transfersome(R) (2.5 micro g cm-2) was bioequivalent to 25 micro g cm-2 TAC in conventional formulations as measured by erythema suppression (cream: P = 0.01, ointment: P < 0.001). A skin blanching assay revealed different kinetics of the formulations, with a delayed onset of action of the Transfersome and ointment preparations. Ultrasonic measurements revealed a significantly reduced atrophogenic potential. There was a 12.1% reduction in skin thickness given by TAC in Transfersome compared with a 21.1% reduction given by a bioequivalent dose in TAC cream after a 6-week treatment period (P = 0.007). CONCLUSIONS: Transfersome may significantly improve the risk-benefit ratio of topically applied glucocorticosteroids.

Administration, Topical↗
PubMed2003

[Cirurgia Taurina--emergency medical treatment of bullfighters in Spain].

A considerable risk of life-threatening injury is inherent to bullfighting. Thus, a unique form of emergency treatment has evolved over recent decades of organized bull-fighting. Today bullfight arenas in larger cities are equipped with emergency facilities including fully furnished operating rooms. During a fiesta these facilities are run by a medical team consisting of three surgeons, one intensive care specialist, and one anesthesiologist with their supporting medical personnel. In smaller arenas or villages immediate care units consist of emergency vehicles, and a mobile container equipped with a fully functional operating room. Of all toreros the matadores including the novilleros are most often injured in 56 % of cases. This rate decreases for banderillos (30 %), and for picadores (14 %). Parts of the body that are most frequently affected are thighs, and the inguinal region (54 %). Head and neck injuries are seen in 19 %, and 12 % of cases present with open abdominal wounds including liver or gastrointestinal tract traumas. 10 % of injuries affect the thorax, and 4 % the pelvic floor. The particular form of organised medical treatment for bullfighters in Spain has only developed since the nineteen-thirties. In 1972 a scientific society for bullfight surgery was founded in Spain by specialized surgeons, and immediate care specialists holding a first convention that year. The society is continuously striving to improve technical and logistical aspects of immediate medical care for injured bullfighters.

Animals↗
PubMed2003

Tree species of the Central Amazon and soil moisture alter stable isotope composition of nitrogen and oxygen in nitrous oxide evolved from soil.

The use of stable isotopes of N and O in N2O has been proposed as a way to better constrain the global budget of atmospheric N2O and to better understand the relative contributions of the main microbial processes (nitrification and denitrification) responsible for N2O formation in soil. This study compared the isotopic composition of N2O emitted from soils under different tree species in the Brazilian Amazon. We also compared the effect of tree species with that of soil moisture, as we expected the latter to be the main factor regulating the proportion of nitrifier- and denitrifier-derived N2O and, consequently, isotopic signatures of N2O. Tree species significantly affected delta15N in nitrous oxide. However, there was no evidence that the observed variation in delta15N in N2O was determined by varying proportions of nitrifier- vs. denitrifier-derived N2O. We submit that the large variation in delta15N-N2O is the result of competition between denitrifying and immobilizing microorganisms for NO3(-). In addition to altering delta15N-N2O, tree species affected net rates of N2O emission from soil in laboratory incubations. These results suggest that tree species contribute to the large isotopic variation in N2O observed in a range tropical forest soils. We found that soil water affects both 15N and 18O in N2O, with wetter soils leading to more depleted N2O in both 15N and 18O. This is likely caused by a shift in biological processes for 15N and possible direct exchange of 18O between H2O and N2O.

Brazil↗
PubMed2003

Wire or coated balloon? Searching for an optimal source for intravascular brachytherapy with beta emitters using (32)P as an example.

This study identifies basic dosimetric differences between two designs for intravascular brachytherapy (IVBT) in current clinical practice and ongoing trials and their clinical implications within beta emitting systems using P-32 as an example. The two designs are (i) the wire-type source, where the radioactive source material is confined to a wirelike structure within the vessel lumen, and (ii) the balloon-surface source, where the radioactive source material is distributed over a surface area (balloon-wall) which is brought in close proximity with the vessel wall. Using Monte Carlo simulations with the EGS4 code, the target coverage, the influence of centering errors, and the perturbation of the dose distribution caused by metallic stents have been compared. The radial dose fall-off in the target region was found to be steeper for balloon surface systems compared with wire systems. The inner lumen wall dose for a balloon surface source was 25% higher than that for a wirelike source (2.5 mm vessel diameter). However, the comparably shallower fall-off from wire-type systems is very sensitive to centering uncertainties. A 0.5 mm displacement, for example, will cause the dose to change by a factor of 2 at the inner vessel wall and by a factor of 1.8 at the prescription point. It is shown that the interference from metallic stents is more significant for wire-type systems than it is for balloon-surface-type systems, where double the dose variation beyond the stent at the radial prescription distance may occur. Centering uncertainties dominate the dose perturbation effects for wire-type systems. Balloon-surface-type designs show a more predictable dose distribution that features, however, a higher inner vessel surface dose. Since a direct clinical comparison of systems of both types is not likely, these findings should be considered when interpreting clinical results from treatments with either type of source and, possibly, for future source design.

Beta Particles↗
PubMed2003

[Systemic chemotherapy for transitional cell carcinoma of the urothelium].

Moderate activity of systemic chemotherapy for advanced urothelial cancer has been reported for more than 30 years. Only with the advent of potent combination therapy in the mid eighties of the past century clinically significant response rates as well as prolonged survival has been documented. This review summarizes seven Phase-III trials of systemic chemotherapy for advanced urothelial carcinoma as well as results from adjuvant and neoadjuvant Phase-III trials for muscle-invasive bladder cancer including the most recent reports.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Gemcitabine in advanced bladder cancer].

MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) has been the standard treatment for patients with advanced urothelial cancer for more than 15 years. Combination chemotherapy including gemcitabine/cisplatin showed similar tumor response and survival rates with a more tolerable toxicity profile in a recent multinational phase III study when compared to MVAC. Effectiveness of gemcitabine as a single agent or in combination with other cytotoxic agents had been investigated before in several phase II studies treating patients with advanced urothelial cancers. The tumor response rate for single agent gemcitabine in advanced urothelial cancers is between 11% and 28%. Tumor response rates rise to 50% when combining gemcitabine with cisplatin, and median survival times between 12 and 15 months can be expected. Triplet therapy schedules including gemcitabine may yield response rates in up to 80% of patients, particularly when used sequentially with other regimens. Further improvement of tolerability during systemic gemcitabine/cisplatin combination therapy without compromising effectiveness was recently demonstrated by a German phase II study when the 4-week schedule was reduced to a 3-week schedule with gemcitabine given on days 1 and 8.

Antimetabolites, Antineoplastic↗
PubMed2002

Microflora reactive IL-10 producing regulatory T cells are present in the colon of IL-2 deficient mice but lack efficacious inhibition of IFN-gamma and TNF-alpha production.

BACKGROUND: Inflammatory bowel disease in interleukin 2 (IL-2) deficient (IL-2(-/-)) mice is triggered by the intestinal microflora and mediated by CD4(+) T cells. AIMS: To determine the characteristics of microflora specific intestinal T cells, including migration and cytokine production. METHODS: Intestinal T cell populations and cytokine mRNA expression of specific pathogen free (SPF) and germ free (GF) IL-2(-/-) and IL-2(+/+) mice were compared by flow cytometry and reverse transcription-polymerase chain reaction. Cytokine production of intestinal mononuclear cells on stimulation with microflora antigens was assessed by ELISA. In vivo migration of T cells was assessed by adoptive transfer of (51)Cr labelled CD4(+)CD25(-)alpha beta(+) T cells. The ability of intestinal T cell lines to promote colitis was determined by adoptive transfer experiments. RESULTS: SPF IL-2(-/-) mice produced higher interferon gamma (IFN-gamma) and tumour necrosis factor alpha mRNA levels than GF IL-2(-/-) mice, which was accompanied by an increased number of CD4(+)alpha beta T cells in the colon. Tracking of (51)Cr labelled and adoptively transferred T cells revealed an increased MAdCAM-1 dependent but VCAM-1 independent recruitment of these cells into the colon of SPF IL-2(-/-) mice. Colon lamina propria lymphocytes (LPL) from SPF IL-2(-/-) mice showed increased spontaneous IFN-gamma production in vitro. On stimulation with bacterial microflora antigens, intraepithelial lymphocytes and LPL did not produce IFN-gamma, but high quantities of IL-10, which did not suppress IFN-gamma production. Bacterial antigen specific cell lines established from colon LPL of SPF IL-2(-/-) mice with colitis showed a regulatory T cell-like cytokine profile and only marginally modulated the course of colitis and survival of IL-2(-/-) mice. CONCLUSIONS: Our results suggest that microflora reactive regulatory T cells are present in the colon of SPF IL-2(-/-) mice. However, IL-10 produced by these cells did not significantly modulate a possible secondary proinflammatory CD4 Th1 cell population to produce IFN-gamma.

Adoptive Transfer↗
PubMed2002

Intraoperative intra-arterial urokinase therapy after failed embolectomy in acute lower limb ischemia.

BACKGROUND: Aim of this study is to evaluate the use of intraoperative intra-arterial urokinase infusion (IIUI) in overcoming residual thrombi after thromboembolectomy in acute lower limb ischemia. METHODS DESIGN: retrospective study over a 3-year period. SETTING: University affiliated hospital. PATIENTS: 21 patients with acute lower limb ischemia who underwent IIUI after embolectomy (18 transfemoral, 3 transpopliteal) had failed to achieve adequate distal perfusion. Postoperatively, all patients were maintained on full dose heparinization. MAIN OUTCOME MEASUREMENTS: complete or partial clot lysis on post-IIUI angiography; restoration of pedal pulses and a viable leg at discharge. RESULTS: Angiographically, complete and partial lysis was demonstrated in 14 and 3 patients, respectively. Two patients with prolonged ischemia required fasciotomy. One of these eventually had an amputation. Altogether, limb amputations (1 above knee, 2 below knee) were necessary in 3 patients. The angiographic appearance of lysis correlated well with the restoration of pedal pulses and/or limb viability. One patient died of myocardial infarction 3 days after the procedure. Postoperatively, there were 5 (24%) wound hematomas of which 1 required surgical exploration. Over a mean follow-up period of 8 months (range 1-16), limb salvage was sustained in the 17 patients with successful angiographic lysis. CONCLUSIONS: IIUI is an effective therapeutic adjunct to failed embolectomy in acute lower limb ischemia. Use of this procedure is recommended as part of the routine management in such cases.

Aged↗
PubMed2001

IL-12p40-dependent agonistic effects on the development of protective innate and adaptive immunity against Salmonella enteritidis.

To study a potential IL-12p40-dependent but IL-12p75-independent agonistic activity regulating the immune response against Salmonella Enteritidis, the course of infection in IL-12p35-deficient mice (IL-12p35(-/-), capable of producing IL-12p40) was compared with that of IL-12p40(-/-) mice. Mice lacking IL-12p40 revealed a higher mortality rate and higher bacterial organ burden than mice capable of producing IL-12p40. This phenotype was found in both genetically susceptible (BALB/c, Ity(s)) and resistant mice (129Sv/Ev, Ity(r)) indicating Ity-independent mechanisms. The more effective control of bacteria in the IL-12p35(-/-) mice was associated with elevated serum IFN-gamma and TNF-alpha levels. In contrast, IL-12p40(-/-) mice showed reduced IFN-gamma production, which was associated with significantly elevated serum IgE levels. Early during infection (days 3 and 4 postinfection), as well as late (day 20 postinfection), the number of infected phagocytes was strongly increased in the absence of IL-12p40 indicating impaired bactericidal activity when IL-12p40 was missing. Liver histopathology revealed a decreased number of mononuclear granulomas in IL-12p40(-/-) mice. Depletion of CD4(+) or CD8(+) T lymphocytes in vivo suggested that both T cell subpopulations contribute to the IL-12p40-dependent protective functions. Analysis of IL-12p40 vs IL-23p19 mRNA expression revealed an up-regulation of only IL-12p40 mRNA during Salmonella infection. Together these data indicate that IL-12p40 can induce protective mechanisms during both the innate and the adaptive type 1 immune response in Salmonella infection. This novel activity of IL-12p40 complements the well described dominant and essential role of IL-12p75 in protective immunity to Salmonella infection.

Animals↗
PubMed2001

An automatic system for the assessment of complex medium additives under cultivation conditions.

Complex medium additives such as yeast extract or peptone are often used in industrial cell culture processes to prolong cell growth and/or to improve product formation. The quality of those supplements is dependent on the preparation method and can differ from lot to lot. To guarantee consistent production these different lots have to be tested prior to use in fermentation processes. Because a detailed qualitative and quantitative analysis of all components of such a complex mixture is a very difficult task, another assessment method has to be chosen. The best way to evaluate the effect of such supplements is to monitor cell activity during real cultivation conditions with and without the added supplement lot. A bioreactor-based test system has been developed to determine the oxygen requirement of the cells as a response to the addition of a supplement to be tested under standardized conditions. Investigations were performed with a mouse-mouse hybridoma cell line and yeast extracts as an example for complex medium additives. The results showed differences in the impact between different extract lots and between different concentrations of an extract.

Animals↗
PubMed2001

Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki ).

The purpose of this study was to determine, as we did for paclitaxel, the cytotoxic and radiosensitizing potential of docetaxel in human head and neck cancer cells (ZMK-1), and in cervical squamous cell carcinoma cells (CaSki). ZMK-1 cells were incubated with docetaxel for 3, 9 or 24 hr before irradiation and 24 hr after irradiation. CaSki cells were incubated with docetaxel 24 hr before and after irradiation. For ZMK-1 cells, the docetaxel concentrations (0.7, 0.7 and 0.35 nM) were determined to obtain approximately equivalent cell survival at the different incubation times (3, 9 and 24 hr, respectively). For CaSki cells, the necessary concentration of docetaxel was 0.07 nM. Radiation doses were given from 0 to 7 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of docetaxel to accumulate cells in the G2/M phase of the cell cycle. We observed a weak accumulation of cells in the G2/M phase for the ZMK-1 cells and a pronounced accumulation for CaSki cells. For docetaxel incubation before irradiation, the isoeffect enhancement ratios for ZMK-1 cells determined at the 37% survival level were 1.18, 2.01, and 2.40 for pre-incubation at 3, 9 and 24 hr, respectively; for CaSki cells the ratio was 1.44. For a docetaxel incubation of 24 hr after irradiation, the isoeffect enhancement ratios determined at the 37% survival level were 1.54 and 1.17 for the ZMK-1, and CaSki cells, respectively. A radiosensitizing effect of docetaxel could be demonstrated unambiguously in the two cell lines used. In contrast to our previously published results with paclitaxel, docetaxel seems to be a better radiosensitizer than paclitaxel.

Carcinoma, Squamous Cell↗
PubMed2001

Synthesis and cyclooxygenase inhibitory properties of novel (+) 2-(6-methoxy-2-naphthyl)propanoic acid (naproxene) derivatives.

Halomethylation of naproxene (1) occurs regioselectively in position 5 and subsequently--in situ or on treatment with silver nitrate--leads to naproxene-"dimers" with two naproxene units, 5,5'-connected through a ethenylene (3) and a methylene (4) bridge, respectively. Two of the new naproxene derivatives were screened for their cyclooxygenase inhibitory properties relative to naproxene. Both 5-chloromethyl naproxene (2) and 2-(5-((carboxyethyl)-2-methyloxynaphthyl)-6-methoxy-2-naphthyl)propanoic acid (4) were inactive in the concentration range of 0.1-10 mumole against both COX-1 and COX-2, indicating that bulky substituents in position 5 in naproxene are unfavourable for both COX-1 and COX-2 inhibition.

Cyclooxygenase 1↗
PubMed2001

Synthesis and 5-HT2A antagonist activity of derivatives of the novel heterocycles indolo[3,2-d]pyrrolo[3,2-g]azecine and benzo[d]pyrrolo[3,2-g]azecine compared to the benz[d]indolo[2,3-g]azecine derivative LE 300.

An indolo[3,2-d]pyrrolo[3,2-g]azecine and a benzo[d]pyrrolo[3,2-g]azecine analogue of the potent dopamine receptor antagonist LE 300 (7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine) have been prepared in multi-step reactions via C-N bond cleavage of corresponding quaternary N-methylquinolizinium iodides. LE 300, the target compounds and two precursor quinolizines have been tested in vitro for antagonist activity at 5-HT2A receptors (rat tail artery) and H1 receptors (guinea-pig ileum), respectively. LE 300 and compound 19 (3,6-dimethyl-4,5,6,7,8,13-hexahydro-3H-benzo[d]pyrrolo[3,2-g]azecine) competitively inhibited 5-HT-induced contractions with similar nanomolar potency (pA2 = 8.32 and 8.01, respectively) but were less active than the reference antagonist ketanserin (pA2 = 9.55). Compound 19 displayed moderate H1-antihistaminic activity in the guinea-pig ileum assay (pA2 = 7.37).

Animals↗