Enhancement of skin radical scavenging activity and stratum corneum lipids after the application of a hyperforin-rich cream.

Hyperforin is well-known for its anti-inflammatory, anti-tumor, anti-bacterial, and antioxidant properties. The application of a hyperforin-rich verum cream could strengthen the skin barrier function by reducing radical formation and stabilizing stratum corneum lipids. Here, it was investigated whether topical treatment with a hyperforin-rich cream increases the radical protection of the skin during VIS/NIR irradiation. Skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, the absorption- and scattering coefficients, which influence radical formation, were determined. 11 volunteers were included in this study. After a single cream application, VIS/NIR-induced radical formation could be completely inhibited by both verum and placebo showing an immediate protection. After an application period of 4weeks, radical formation could be significantly reduced by 45% following placebo application and 78% after verum application showing a long-term protection. Furthermore, the skin lipids in both verum and placebo groups increased directly after a single cream application but only significantly for ceramide [AP], [NP1], and squalene. After long-term cream application, concentration of cholesterol and the ceramides increased, but no significance was observed. These results indicate that regular application of the hyperforin-rich cream can reduce radical formation and can stabilize skin lipids, which are responsible for the barrier function.

Model-free fMRI group analysis using FENICA.

Exploratory analysis of functional MRI data allows activation to be detected even if the time course differs from that which is expected. Independent Component Analysis (ICA) has emerged as a powerful approach, but current extensions to the analysis of group studies suffer from a number of drawbacks: they can be computationally demanding, results are dominated by technical and motion artefacts, and some methods require that time courses be the same for all subjects or that templates be defined to identify common components. We have developed a group ICA (gICA) method which is based on single-subject ICA decompositions and the assumption that the spatial distribution of signal changes in components which reflect activation is similar between subjects. This approach, which we have called Fully Exploratory Network Independent Component Analysis (FENICA), identifies group activation in two stages. ICA is performed on the single-subject level, then consistent components are identified via spatial correlation. Group activation maps are generated in a second-level GLM analysis. FENICA is applied to data from three studies employing a wide range of stimulus and presentation designs. These are an event-related motor task, a block-design cognition task and an event-related chemosensory experiment. In all cases, the group maps identified by FENICA as being the most consistent over subjects correspond to task activation. There is good agreement between FENICA results and regions identified in prior GLM-based studies. In the chemosensory task, additional regions are identified by FENICA and temporal concatenation ICA that we show is related to the stimulus, but exhibit a delayed response. FENICA is a fully exploratory method that allows activation to be identified without assumptions about temporal evolution, and isolates activation from other sources of signal fluctuation in fMRI. It has the advantage over other gICA methods that it is computationally undemanding, spotlights components relating to activation rather than artefacts, allows the use of familiar statistical thresholding through deployment of a higher level GLM analysis and can be applied to studies where the paradigm is different for all subjects.

Comparison of two different odorants in an olfactory detection threshold test of the Sniffin’ Sticks.

The olfactory test battery Sniffin' Sticks is a test of nasal chemosensory function that is based on pen-like devices for odour presentation. It consists of three olfactory subtests: threshold, discrimination, and identification. The detection threshold can be measured using two different odorants--n-butanol or PEA (phenylethyl alcohol). Both tasks are commonly applied in published studies, but little is known about the formal comparison of values obtained using them. Unlike the Sniffin' Sticks with n-butanol as odorant, there is poor validation for the threshold subtest with the odorant PEA. The purpose of this study was to compare these two different odorants. Both odorants were applied to 100 normosmic, healthy subjects (50 females). The experiment was divided into two sessions performed on two different days. After each threshold test the discrimination and identification subtests were conducted. We obtained significant differences in detection thresholds of PEA and n-butanol. The mean score of PEA threshold and PEA TDI (sum of threshold, discrimination, identification) was significantly higher compared to n-butanol. No significant correlation between individual PEA and n-butanol thresholds was observed. The differences between both odorants indicate that a formal validation of the Sniffin' Sticks with PEA as odorant for probing olfactory thresholds may be required.

Potential impact of a 32-channel receiving head coil technology on the results of a functional MRI paradigm.

PURPOSE: The authors investigated the potential of a 32-channel (32ch) receiving head coil for functional magnetic resonance imaging (fMRI) compared to a standard eight-channel (8ch) coil using a motor task. MATERIAL AND METHODS: Brain activation was analyzed in 14 healthy right-handed subjects performing finger tapping with the right index finger (block design) during two experimental sessions, one with the 8ch and one with the 32ch coil (applied in a pseudorandomized order). Additionally, a phantom study was performed to compare signal-to-noise ratios (SNRs) of both coils. RESULTS: During both fMRI sessions, analysis of motor conditions resulted in an activation of the left "hand knob" (precentral gyrus). Application of the 32ch coil obtained additional activation clusters in the right cerebellum, left superior frontal gyrus (SMA), left supramarginal gyrus, and left postcentral gyrus. The phantom study revealed a significantly higher SNR for the 32ch coil compared to the 8ch coil in superficial cortical areas located near the surface of the brain. CONCLUSION: The 32ch technology has a potential impact on fMRI studies, especially in paradigms that result in activation of cortical areas located near the surface of the brain.

Bad mood--bad activation? : The influence of emotions on the BOLD signal during finger tapping.

PURPOSE: The aim of this study was to investigate the influence of the subject's emotional state on the BOLD signal during simple finger tapping. MATERIAL AND METHODS: Twenty-nine healthy subjects participated in three functional magnetic resonance imaging (fMRI) sessions each. The sessions differed regarding emotional states, which were induced by standardized pleasant (positive condition, POS), unpleasant (negative condition, NEG), or neutral (neutral condition, NEU) pictures taken from the International Affective Picture System (IAPS) while the subjects performed a finger-tapping task (right index-to-thumb opposition). After each session, the subjects had to rate their actual mood and the pleasantness of the presented pictures. Furthermore, their state anxiety was assessed. Behavioral data were evaluated with SPSS. Functional imaging data were processed using statistical parametric mapping (SPM2) and were analyzed for main effects of emotional stimulation using an analysis of variance (ANOVA). The local maximum of interest was analyzed by a signal change analysis. RESULTS: Compared to the neutral emotional state, the positive and the negative emotional states caused a reduction of signal intensity changes within the primary sensorimotor hand area during simple finger tapping. The behavioral data indicated that the unpleasant pictures had a stronger effect on the emotional state than the pleasant images. According to these data the decrease in signal intensity change was more pronounced (significant; p < 0.001) in the negative condition than in the positive condition. CONCLUSION: This study showed that the emotional state of a test person is indeed influencing fMRI results and that well-balanced subjects in a neutral mood achieve the best fMRI results.

Chemosensory properties of human sweat.

Human sweat contains a mixture of odorants with trigeminal as well as olfactory properties. It has been shown that trigeminal perception is necessary to localize odors and that humans are not able to localize substances that only activate the olfactory system. To analyze the chemosensory properties of human sweat, we studied humans' ability to localize sweat stimuli to the different nostrils. Human sweat was collected during a bicycle workout (20 males) and was then applied to 34 different subjects (17 females) during odor detection and localization experiments by using an olfactometer. During the detection experiment, subjects were instructed to discriminate between sweat stimuli (20) and blanks (10). During the localization experiment, they were assigned to allocate the stimuli to either the right (15) or the left nostril (15). We found that subjects were able to detect the sweat stimuli with moderate to high sensitivity. However, they failed to localize the sweat stimuli to the accurate nostril above chance level. Due to this inability to localize the stimuli, we conclude that human sweat does not activate the intranasal trigeminal system but only the olfactory system.

Effects of laserneedle acupuncture on olfactory sensitivity of healthy human subjects: a placebo-controlled, double-blinded, randomized trial.

The aims of the present study were to investigate the influence of laserneedle acupuncture on olfactory sensitivity and to examine whether the attitude towards laserneedle acupuncture affects the outcome. Olfaction was tested repeatedly on two days using the olfactory detection threshold subtest of the Sniffin' Sticks test battery in sixty-four healthy subjects of which 32 showed a positive attitude towards the effects of laserneedle acupuncture and 32 were sceptic about its effects. Testing was accomplished three times on day one (T1 = 0 min, T2 = 35 min, T3 = 105 min) without laserneedle acupuncture and on day two (T1* = 0 min, T2* = 35 min, T3* = 105 min) when the subjects were randomized in a non-stimulation (placebo) and a stimulation (laserneedle acupuncture) group. Stimulation or non-stimulation was conducted in a double-blinded design. Following laserneedle acupuncture a significant decrease in olfactory detection thresholds was observed at both, T2* and T3*, whereas no significant changes were found in the baseline or placebo group. Effects of laserneedle acupuncture on the olfactory detection threshold did not differ between sceptic and non-sceptic subjects. In conclusion, laserneedle acupuncture is an effective method to improve olfactory sensitivity after one session of stimulation for at least one hour, independently of the attitude of subjects towards the stimulation method.

Olfactory detection thresholds and pleasantness of a food-related and a non-food odour in hunger and satiety.

The primary aim of this study was to investigate whether olfactory detection thresholds are dependent on different states of satiety. Using the threshold test of the Sniffin' Sticks test battery (single-staircase, three alternative forced choice procedure), sensitivity to a non-food odour (n-butanol) and a food-related odour (isoamyl acetate) was investigated. Twenty-four healthy, female subjects (mean age 24.2 years, SD 2.7 years) with normal olfactory function performed the tests when hungry and when satiated. Additionally, they rated their emotional condition, arousal, alertness as well as the intensity and pleasantness of both odorants. No significant change in the detection thresholds for the non-food odour n-butanol, but a significant change in detection threshold for the food-related odour isoamyl acetate was found. The detection threshold for isoamyl acetate was significantly lower in the state of satiety compared to the hungry condition. As expected, the perceived pleasantness of isoamyl acetate was significantly lower in satiety. In summary, the results indicate that in our experimental setting the actual state of satiety has effects on detection thresholds of a food-related odour, but not of a non-food odour. Interestingly, the higher sensitivity was found during the state of satiety challenging the current hypothesis that control of food intake is supported by a decrease in sensitivity to food odours. Instead our findings that satiety decreases the pleasantness of a food-related odour support the hypothesis that both odour threshold as well as pleasantness play an important role in the control of food intake.

Trigeminal perception is necessary to localize odors.

The human ability to localize odorants has been examined in a number of studies, but the findings are contradictory. In the present study we investigated the human sensitivity and ability to localize hydrogen sulphide (H(2)S), which in low concentrations stimulates the olfactory system selectively, the olfactory-trigeminal substance isoamyl acetate (IAA), and the trigeminal substance carbon dioxide (CO(2)). A general requirement for testing of localization was the conscious perception of the applied stimuli by the participants. Using Signal Detection Theory, we determined the human sensitivity in response to stimulation with these substances. Then the subjects' ability to localize the three different substances was tested. We found that humans can detect H(2)S in low concentration (2 ppm) with moderate sensitivity, and possess a high sensitivity in response to stimulation with 8 ppm H(2)S, 17.5% IAA, 50% v/v CO(2). In the localization experiment, subjects could localize neither the low nor the high concentration of H(2)S. In contrast, subjects possessed the ability to localize IAA and CO(2) stimuli. These results clearly demonstrate that humans, in spite of the aware perception, are not able to localize substances which only activate the olfactory system independent of their concentration, but they possess an ability to localize odorants that additionally excite the trigeminal system.

Investigation of breathing parameters during odor perception and olfactory imagery.

Compared with visual and auditory imagery, little is known about olfactory imagery. There is evidence that respiration may be altered by both olfactory perception and olfactory imagery. In order to investigate this relationship, breathing parameters (respiratory minute volume, respiratory amplitude, and breathing rate) in human subjects during olfactory perception and olfactory imagery were investigated. Fifty-six subjects having normal olfactory function were tested. Nasal respiration was measured using a respiratory pressure sensor. Using an experimental block design, we alternately presented odors or asked the subjects to imagine a given smell. Four different pleasant odors were used: banana, rose, coffee, and lemon odor. We detected a significant increase in respiratory minute volume between olfactory perception and the baseline condition as well as between olfactory imagery and baseline condition. Additionally we found significant differences in the respiratory amplitude between imagery and baseline condition and between odor and imagery condition. Differences in the breathing rate between olfactory perception, olfactory imagery, and baseline were not statistically significant. We conclude from our results that olfactory perception and olfactory imagery both have effects on the human respiratory profile and that these effects are based on a common underlying mechanism.

Cerebral differences in explicit and implicit emotional processing--an fMRI study.

The processing of emotional facial expression is a major part of social communication and understanding. In addition to explicit processing, facial expressions are also processed rapidly and automatically in the absence of explicit awareness. We investigated 12 healthy subjects by presenting them with an implicit and explicit emotional paradigm. The subjects reacted significantly faster in implicit than in explicit trials but did not differ in their error ratio. For the implicit condition increased signals were observed in particular in the thalami, the hippocampi, the frontal inferior gyri and the right middle temporal region. The analysis of the explicit condition showed increased blood-oxygen-level-dependent signals especially in the caudate nucleus, the cingulum and the right prefrontal cortex. The direct comparison of these 2 different processes revealed increased activity for explicit trials in the inferior, superior and middle frontal gyri, the middle cingulum and left parietal regions. Additional signal increases were detected in occipital regions, the cerebellum, and the right angular and lingual gyrus. Our data partially confirm the hypothesis of different neural substrates for the processing of implicit and explicit emotional stimuli.

Effects of lovastatin on progression of non-dilated and dilated coronary segments and on restenosis in patients after PTCA. The cholesterol lowering atherosclerosis PTCA trial (CLAPT).

OBJECTIVES: The Cholesterol Lowering Atherosclerosis PTCA Trial (CLAPT) is a prospective, randomized trial with blinded angiographic end-points to assess the effect of 2-year's treatment with lovastatin initiated 4 weeks prior to PTCA, compared to usual care on non-dilated coronary segments and on dilated coronary lesions in male patients with total cholesterol between 200 and 300 mg. dl(-1)who underwent elective PTCA. METHODS AND RESULTS: Two hundred and twenty six patients were randomized 4 weeks prior to PTCA to special care (diet plus lovastatin n=112) or usual care (diet; n=114). One hundred and ninety-nine patients underwent PTCA at baseline and were finally included in the study. Quantitative coronary angiographic assessment was performed on blinded cinefilms at baseline (PTCA) and repeated after 4 and 24 months in 91% and 81% of the patients. The primary end-point was a change in the mean segment diameter of non-dilated segments. The mean lovastatin dose was 33 mg. day(-1). Total- and LDL-cholesterol decreased by 21% and 29% in the special care group and by 7% and 11% in the usual care patients. After 2 years, the mean segment diameter of non-dilated segments decreased by 0.03 mm in the usual care group and 0.004 mm in the special care group (P=0.27). The decrease in the mean segment diameter of dilated lesions was 0.17 mm (usual care) and 0.06 mm (special care) (P=0.04) after 4 months; 0.16 mm (usual care) and 0. 002 mm (special care) after 24 months, respectively (P=0.05). In both groups, the mean segment diameter of dilated lesions increased between 4 and 24 months after PTCA compared to a decrease in mean segment diameter of non-dilated segments (P<0.05). Restenosis (>50% diameter stenosis at follow-up) occurred in 28.4% of usual care and 22.2% of special care patients (P=0.17). CONCLUSIONS: Lovastatin reduced the progression of dilated lesions in men with elective PTCA. Independent of treatment allocation, the dilated lesions regressed and the non-dilated segments progressed during the study follow-up. Four weeks of pre-treatment with lovastatin did not influence the rate of restenosis. Lovastatin had no statistically significant effect on non-dilated segments.

Failure to confirm ferritin and caeruloplasmin as risk factors for the angiographic extent of coronary arteriosclerosis.

BACKGROUND: It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for coronary artery disease (CAD). Recent studies have reported conflicting data on the role of ferritin and other parameters of oxidative metabolism in CAD. OBJECTIVE: The aim of this study was to assess the relation between the extent of CAD and parameters of oxidation. METHODS: We studied 275 patients (208 men aged 55.1 +/- 9.6 years and 67 women aged 54.6 +/- 10.0 years) who underwent coronary angiography or percutaneous transluminal coronary angioplasty for the first time. The parameters assessed were: iron, ferritin, transferrin, copper, caeruloplasmin and lipid. Cinefilms were assessed by the use of three scores: (1) Vessel score: 0-3 points; 1 point for each of the three main coronary arteries with a stenosis >70%. (2) Stenosis score: 0-32 points; the coronary artery tree was divided into eight segments that were scored 1-4 points per segment with respect to the maximal degree of stenosis. (3) Extent score: 0-100 points; extent of diffuse coronary lesions in each segment in relation to the length of the vessel. Multiple regression analyses were used to evaluate the results. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (P < 0.001) in women, low-density lipoprotein cholesterol (P < 0.05) in men, and patient age showed a significant correlation with all three scores, but none of the parameters of oxidative metabolism (iron, transferrin, ferritin, copper, caeruloplasmin) correlated significantly with any of the three scores. CONCLUSION: This study demonstrated a correlation between lipoproteins and the angiographic extent of CAD, but did not confirm a role for serum ferritin and other oxidative parameters as risk factors for the extent of CAD.

[Qualitative comparison of modified neurolept-, balanced and intravenous anesthesia. 2. Results of a clinical study, 1992]. / Qualitätsvergleich von modifizierter Neurolept-, balancierter und intravenöser Anästhesie. Teil 2. Ergebnisse der Krefelder Studie 1992.

The safety and tolerance of neuroleptanaesthesia (NLA), balanced anaesthesia (BAL), and intravenous anaesthesia with propofol (IVA) were analysed for the first time in a prospective, randomised clinical trial. METHODS. In all, 1318 surgical patients received either NLA, BAL, or IVA. Patients who had regional anaesthesia, were aged under 18 years, or were non-cooperative or vitally threatened (ASA class i.v. to V) did not participate in the study. Premedication and anaesthetic course were set up at a standard of 30% oxygen and 70% nitrous oxide. Incidents, events, and complications due to anaesthesia were obtained (IEC key of the German Society of Anaesthesia and Critical Care Medicine, DGAI). Furthermore, postanaesthetic alertness based on specific recovery tests and the quality of anaesthesia from the patient's viewpoint, rated by patient questionnaires from the DGAI were evaluated. All parameters were calculated and checked for statistical significance using the chi-square test. RESULTS AND DISCUSSION. The groups were broadly comparable with respect to age (P = 0.91), ASA class (P = 0.42), preoperative blood pressure (P = 0.36), and length of anaesthesia (P = 0.82). The anaesthesia, which averaged 103 min, comprised the following regimens: (1) NLA: 7.1 mg droperidol and 0.008 mg/kg body weight fentanyl, (2) IVA: 493.4 mg propofol and 0.004 mg/kg body weight fentanyl, and (3) BAL: 2.6 mg droperidol and 0.004 mg/kg body weight fentanyl with 0.4 vol.% isoflurane. With respect to anaesthetic risk, the following reactions were observed: the use of NLA led to a high incidence of tachycardia (P = 0.001), arrhythmias (P = 0.05), and hypertensive reactions (P = 0.001), whereas in the IVA group only hypotension (P = 0.0001) occurred. However, after the use of BAL none of the aforementioned complications were detectable to any considerable degree. Similarly, patients who had cardiac disease showed greater IEC changes after the use of NLA than after BAL or IVA (P = 0.02) (Tables 1 and 2). The heart rates and blood pressures during BAL and IVA were extremely stable, and therefore, vasoactive therapy was required considerably less in comparison to NLA (P = 0.001) (Table 4). Recovery after the use of IVA was strikingly rapid: the patient's responsiveness, orientation, and ability to concentrate was significantly better than after the other anaesthetic regimen (P = 0.01) (Table 5). With regard to the typical discomforts after anaesthesia, IVA was highly superior to BAL and NLA: nausea (P = 0.0003) and retching (P = 0.03) hardly ever occurred (Table 6). Due to the tolerable manner of waking up and rapid return of orientation and the ability to concentrate, IVA was highly favoured by the patients (P = < 0.01) (Table 7). CONCLUSION. The present results show clear clinical advantages of BAL and IVA in contrast to neuroleptanaesthesia. Due to the very low incidence of side effects such as nausea and vomiting IVA was highly recommended by the patients, at least in part because of the rapid recovery time.

[Quality comparison of modified neurolept-, balanced and intravenous anesthesia. 1. Study design and patient analysis of the Krefelder study 1992]. / Qualitätsvergleich von modifizierter Neurolept-, balancierter und intravenöser Anästhesie. Teil 1. Studiendesign und Patientenanalyse der Krefelder Studie 1992.

The choice of appropriate anaesthesia in a more or less seriously ill patient requires detailed information on the risk and tolerance of each specific anaesthetic regimen. The objective of this prospective, randomised clinical trial was to test the hypothesis that three regimens of general anaesthesia--neurolept-(NLA), balanced (BAL), and intravenous propofol anaesthesia (IVA)--differ with regard to safety and comfort. The criteria for the intraoperative safety and postoperative comfort of the patients were the incidents, events and complications (IEC) that required medical treatment as well as the evaluation of postoperative complaints by the patients according to the IEC list and patient questionnaires of the German Society of Anaesthesia and Critical Care Medicine (DGAI). METHODS. The study duration was about 4 months, from January to April 1992. During this period the patients of all nine operative departments of the hospital received strictly randomised NLA, BAL, or IVA. Patients who had regional anaesthesia or were not capable of understanding the German language, were nonco-operative, or were seriously ill (ASA class IV to V) as well as children under 18 years of age did not participate in the study. All eligible patients provided their informed consent. ANAESTHESIA. For premedication 10 mg chlorazepate was administered the night before and on the day of surgery. Anaesthesia was conducted under normoventilation using a mixture of 70% nitrous oxide and 30% oxygen. NLA patients were induced intravenously with 0.2 mg/kg body weight etomidate and received 0.005 mg/kg fentanyl and 0.07 mg/kg droperidol before the start of surgery. The repetition dose was 0.2 mg fentanyl and 2.5 mg droperidol. In the BAL patients the dose of fentanyl and droperidol was reduced to 50% due to the addition of isoflurane up to 1 vol. %. IVA patients received 2 mg/kg propofol over 3 min followed by an infusion of 3-5 mg/kg per hour together with 0.2 mg fentanyl/h. Neuromuscular blockade was accomplished with vecuronium 0.1 mg/kg. If the blood pressure and heart rate increased by more than 20% of preoperative values, analgesia was reinforced by an additional fentanyl dose. Anaesthesia was subsequently enhanced by increasing the neurolept/propofol/isoflurane dose by up to 50%. DATA COLLECTION. The following parameters were registered: patients' personal data and physical condition according to ASA classification; the grade of risk according to the Munich risk checklist; the frequency of IEC during surgery; the patients' permanent medications; postanaesthetic vigilance and recovery; the acceptance of the assigned anaesthetic by the physician; the cost of the anaesthetic used; and pre- and post-operative complaints as well as the assessment of anaesthesia by the patient. The statistical evaluation was performed using the chi-square test. RESULTS. A total of 1,346 patients were enrolled in the study; 28 (2%) were excluded because the treatment protocol was changed by the anaesthesiologist. Seventy per cent were recruited from general, gynaecologic, or otorhinolaryngologic surgery. The three anaesthetic regimens (NLA, BAL, and IVA) were used in other departments with the same frequency with the exception of ophthalmology and urology (P > 0.1) (Fig. 1). Of the 1,318 eligible patients, 443 received NLA, 443 BAL, and 432 IVA (P = 0.8). The distribution of the various parameters was surprisingly similar among the three groups: the average age was 50 years (P = 0.91), body weight 71 kg (P = 0.33), reference or initial blood pressure 130/80 mm Hg (P = 0.36), average time of anaesthesia 103 min (P = 0.82), and all had the same risk score (P = 0.42). Sixty per cent were female. An average of 85% of the 18- to 89-year-old patients were considered to be healthy according to the ASA risk classification (P = 0.42). However, on applying the Munich risk checklist the average number of healthy individuals was 5% to 10% lower than that of the ASA risk classification.

Synthesis and antitumor activity of two ifosfamide analogs with a five-membered ring.

Two ifosfamide (CAS 3778-73-2) analogs with a five-membered ring, i.e. the oxazaphospholidine derivatives 6 and 7, were synthesized and their cytotoxic activity in vitro, acute toxicity and antitumor activity in vivo determined in comparison with the oxazaphorinane ifosfamide 1. The observed low biological activity gives evidence that both, the six-membered oxazaphosphorinane ring and the two N-2-chloroethyl-side chains are necessary for the generation of the ultimate alkylator, i.e. the ifosfamide mustard 5.

Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.

In the course of studies on tranquilizers, new non-benzodiazepine-like compounds were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2-methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof which were screened pharmacologically in order to evaluate their central nervous system activity. Compounds with marked antiaggressive and anxiolytic properties but without dependence potential could be detected. Enciprazine was selected for clinical investigations.

[Synthesis of germinal 3,3-dithienyl compounds (author's transl)]. / Synthese geminaler 3,3-dithienylverbindungen.

A new synthetic approach to the cerebroactive compound (+)-(R)-alpha-[(S)-1-[(3,3-di-3-thienylallyl)amino]ethyl]benzyl alcohol(1) (tinofedrine), its stereoisomers and related derivatives is reported. Several compounds increased blood flow in the arteriae vertebralis and femoralis of anesthesized dog.