Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 19 recordsLinked to original sources

PubMed1995

Neuronal mechanism of the inhibitory effect of calcitonin on N-methyl-D-aspartate-induced aversive behavior.

To elucidate the mechanism of antinociceptive effects of calcitonin, we investigated whether receptor antagonists for various neurotransmitter receptors alter the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice. Neither naloxone, an opioid receptor antagonist, phentolamine and benextramine, alpha-adrenoceptor antagonists, nor ritanserin, a 5-HT2A receptor antagonist, inhibited the calcitonin-induced anti-aversive effects. Pindolol and (--)-propranolol, non-selective antagonists of beta-adrenoceptors and 5-HT1 receptors, 1-(2-methoxyphenyl)-4-[4-(2-phethalimido) butyl]-piperazine hydrobromide (NAN-190), a 5-HT1A receptor antagonist, 3-tropanyl-3,5-dichlorobenzoate (MDL72222) and metoclopramide, 5-HT3 receptor antagonists, significantly inhibited the calcitonin-induced anti-aversive effects. (--)-Bicuculline, a GABAA receptor antagonist, phaclofen and 5-aminovaleric acid, GABAB receptor antagonists, also attenuated the calcitonin-induced anti-aversive effects. These results suggest that beta-adrenoceptor, 5-HT1A, 5-HT3, GABAA and GABAB receptors, but not alpha-adrenoceptor, opioid nor 5-HT2A receptors, are involved in the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice.

Adrenergic alpha-Antagonists↗

PubMed1995

Activation of both dopamine D1 and D2 receptors necessary for amelioration of conditioned fear stress.

Mice exhibited a marked suppression of motility when they were re-placed in the same environment in which they had previously received an electric footshock. This psychological stress-induced motor suppression, known as conditioned fear stress, was dose dependently attenuated by apomorphine, a non-selective dopamine receptor agonist. Combined treatment with the dopamine D1 receptor agonist, SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1-H-3-benzazepine), and the dopamine D2 receptor agonist, quinpirole, also synergistically attenuated the conditioned fear stress although, alone, neither SKF 38393 nor quinpirole did so at the doses used. The effects of apomorphine and of the coadministration of SKF 38393 and quinpirole on the conditioned fear stress were completely blocked by the dopamine D1 receptor antagonist, SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine), and by the dopamine D2 receptor antagonist, (-)-sulpiride. These results suggest that a dysfunction in the dopaminergic neuronal system is responsible for the conditioned fear stress, and that the activation of both dopamine D1 and D2 receptors is necessary to attenuate this stress-induced motor suppression.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Sustained release of basic fibroblast growth factor from the synthetic vascular prosthesis using hydroxypropylchitosan acetate.

We designed a model vascular prosthesis consisting of expanded polytetrafluoroethylene (Gore Tex) loaded with basic fibroblast growth factor (bFGF), and studied its in vivo bFGF release behavior. To control the release rate of bFGF, biodegradable hydroxypropylchitosan acetate (HPCHA) was also incorporated into the Gore Tex disks with bFGF. HPCHA was dissolved in bFGF solution (180 micrograms/ml) at a concentration of 4% (wt/vol). A Gore Tex tube was cut into a length of about 5 cm and one end was sealed with a vascular clamp. The tube was then filled with resulting solution under appropriate pressure until the solvents seeped through the pores. The tube loaded with bFGF solution was freeze-dried and was cut into disks (0.75 cm in diameter). bFGF content in a HPCHA-free Gore disk was 2.05 +/- 0.32 micrograms (SE, n = 5). bFGF content in a HPCHA Gore disk was 2.71 +/- 0.41 micrograms (SE, n = 5). In an in vivo study in which the bFGF loaded Gore Tex disk was implanted in rabbit skin pockets, almost 100% of bFGF from HPCHA-free disks was released within 24 h, whereas some 60% remained after 24 h in the HPCHA-loaded disks. HPCHA is a useful biodegradable carrier for controlling the release rate of the drug from the synthetic vascular prosthesis.

Animals↗

PubMed1995

Prevention of bone loss by percutaneous estradiol implants in ovariectomized rats.

This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.

Animals↗

PubMed1995

Echo-planar diffusion spectroscopic imaging.

High-speed diffusion spectroscopic imaging based on an echo-planar technique is presented. A pair of diffusion gradients is applied prior to a rapidly oscillating magnetic field gradient which encodes both chemical shift and spatial information. By applying this technique to a phantom consisting of acetone and water, a diffusion spectroscopic image is obtained in about 15 min, about 64 times faster than the time required in the conventional method. The measured diffusion coefficients show good agreement with previously reported values. This kind of diffusion spectroscopic imaging is expected to provide a way to observe more specific metabolism.

Acetone↗

PubMed1995

Risperidone prevents the development of supersensitivity, but not tolerance, to phencyclidine in rats treated with subacute phencyclidine.

We investigated whether risperidone, a 5-HT2/dopamine-D2 receptor antagonist, inhibits the development of tolerance and supersensitivity to PCP and whether subacute administration of PCP with risperidone affects the [3H]MK-801 binding in rat brain, in comparison with dopamine-D2 receptor antagonist haloperidol and 5-HT2 receptor antagonist ritanserin. In rats treated with PCP (10 mg/kg, i.p.) for 14 days, PCP (10 mg/kg, i.p.)-induced hyperlocomotion, rearing and sniffing were potentiated (supersensitivity), and head-weaving, head-twitch, backpedalling and turning were diminished (tolerance). The development of supersensitivity to PCP was blocked by oral co-administration of risperidone (2.4 mg/kg, p.o.) and haloperidol (1.0 mg/kg, p.o.) for 14 days, but not ritanserin (10 mg/kg, p.o.) and risperidone (0.8 mg/kg, p.o.), while no drugs prevented the development of tolerance to PCP. Both risperidone (2.4 mg/kg, p.o.) and haloperidol (1.0 mg/kg, p.o.) also inhibited the cross-supersensitivity to methamphetamine (MAP; 2.5 mg/kg, i.p.)-induced rearing in rats treated with PCP for 14 days. The profiles of [3H]MK-801 binding in discrete brain areas did not change after subacute administration of PCP alone or in combination with risperidone, haloperidol or ritanserin for 14 days. Therefore, it is suggested that subacute administration of PCP may cause functional changes in the dopaminergic neuronal transmission under conditions where the binding of [3H]MK-801 in discrete brain areas is unchanged, and that co-administration of risperidone may block these PCP-induced changes in neuronal function.

Animals↗

PubMed1995

The attenuation of suppression of motility by triazolam in the conditioned fear stress task is exacerbated by ethanol in mice.

We investigated whether triazolam attenuated the suppression of motility in the conditioned fear stress task in mice and whether ethanol modified the effects of triazolam. When mice were placed 24 hours later (retention test) in the same environment in which they had previously been exposed to an electric foot shock (training), they exhibited a marked suppression of motility (conditioned fear stress). Triazolam (0.01-0.1 mg/kg, s.c.), administered before training, attenuated the suppression of motility in the conditioned fear stress task in a dose-dependent manner, without affecting the sensitivity to an electric foot shock. The doses of triazolam that attenuated the suppression of motility were much lower that those of chlordiazepoxide (5-10 mg/kg, s.c.). Neither drug, administered before the retention test, attenuated the suppression of motility in the conditioned fear stress task. These results suggest that both benzodiazepines may inhibit the process of acquisition, but not the process of recall, of memory. Ethanol (1 g/kg, p.o.), which, by itself, did not affect either the suppression of motility or the sensitivity to an electric foot shock, exacerbated the attenuation of the suppression of motility in the conditioned fear stress task induced by both triazolam (0.01 mg/kg) and chlordiazepoxide (5 mg/kg). These results suggest that ethanol exacerbates the effects of benzodiazepines.

Animals↗

PubMed1995

Stress-induced behavioral responses and multiple opioid systems in the brain.

Various stressor produce a wide range of behavioral responses such as analgesia, catalepsy and motor suppression, which are sensitive to opioid receptor antagonists. These behavioral responses in stress are accompanied by changes in the contents of opioid peptides, the mRNAs encoding their precursors and opioid receptor binding in the brain. In the present article, experimental data concerning stress-induced analgesia and motor suppression is reviewed and discussed in relation to a possible involvement of different opioid systems in the various observed behavioral responses in stress. Pharmacological studies with subtype-selective antagonists have demonstrated that not only mu- but also delta- and/or kappa-opioid receptors are involved in opioid-mediated stress-induced analgesia. There are two types of stress-induced analgesia referred to as opioid-mediated and non-opioid mediated forms. It has been proposed that the intensity and temporal pattern of stressor may be a critical factor determining the nature of stress-induced analgesia. Accumulated evidence demonstrate that these two forms of pain inhibitory systems interact each other according to a collateral inhibition model. Recent studies show that parallel activation of multiple opioid receptors mediates non-opioid froms of stress-induced analgesia. Dynorphins, by acting at kappa-opioid receptors, may play a pivotal role in the expression of stress-induced motor suppression, whereas enkephalins may act to attenuate this response.

Adaptation, Psychological↗

PubMed1995

Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain.

1. We investigated the effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on the performance of rats in a radial arm maze and in habituation tasks, and on monoamine metabolism in the brain. 2. Daily administration of L-NAME (10-60 mg kg-1) resulted in a dose-dependent impairment of performance during the acquisition of the radial arm maze task, while it failed to affect performance in those rats that had previously acquired the task. 3. The rate of decrease in locomotor activity in the habituation task in the L-NAME-treated rats was significantly less than that in control rats. 4. NG-nitro-D-arginine methyl ester (D-NAME, a less active inhibitor of NO synthase) showed no effects in the above behavioural tasks. 5. NO synthase activity was significantly decreased in both the L-NAME and D-NAME-treated rats, with the magnitude of inhibition being greater in the L-NAME-treated animals. 6. The content of 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and the 5-HIAA/5-hydroxytryptamine ratio in the hippocampus and cortex were significantly decreased in the L-NAME (60 mg kg-1)-treated rats compared with these values in the controls. 7. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) content was significantly increased in the L-NAME (60 mg kg-1)-treated rats compared with the values in the controls, while the DOPAC/dopamine ratio was not changed. 8. These results suggest that: (i) NO may play an important role in performance during the acquisition,but not retention, of the radial arm maze task, and (ii) that endogenous NO may be involved in the regulation of monoamine metabolism.

Animals↗

PubMed1995

Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia.

1. Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. 2. Repeated treatment with PCP (10 mg kg-1 day-1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg-1, s.c.), or by repeated treatment with methamphetamine (0.5 and 1 mg kg-1 day-1, s.c., once a day for 14 days). 3. The enhancing effect of PCP (10 mg kg-1 day-1, s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 4. Haloperidol (0.3 and 1 mg kg-1, p.o.), ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.1-1 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice repeatedly treated with saline when the drugs were administered 1 h before the forced swimming test. However, ritanserin (30 mg kg-1) and clozapine (30 mg kg-1) did attenuate this immobility. 5. The enhancing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.3 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.), whereas haloperidol (0.3 and 1 mg kg-1, p.o.) had no effect. 6. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors.

Animals↗

PubMed1995

Brain distribution characteristics of xanthine derivatives and relation to their locomotor activity in mice.

The relationship between the brain distribution and motor activity in mice of the xanthines, theophylline, enprofylline, 1-methyl-3-propylxanthine (MPX) and oxpentifylline was investigated. Their plasma protein binding and hydrophobicity were also examined. When these xanthines were administered orally, enprofylline and oxpentifylline had no effect on motor activity. While theophylline increased motor activity over 10 mg kg-1, MPX caused a decrease in such activity over 10 mg kg-1. The protein-binding behaviour varied among these xanthines and was closely related to their hydrophobicity, which is represented as a logarithmic partition coefficient (log PC). MPX had the highest hydrophobicity, while oxpentifylline had the lowest. Brain distribution characteristics varied among these xanthines, with the rank order of their brain penetration ratio, calculated as the ratio of brain to unbound plasma concentrations, being theophylline > oxpentifylline > MPX > enprofylline. The inhibition constants (Ki) for adenosine A1 receptors and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase (PDE) of these xanthines were 44.6 and 134, > 1000 and 112, 26.4 and 49, and > 1000 and 111 microM for theophylline, enprofylline, MPX, and oxpentifylline, respectively. These findings suggest that the lack of effects of enprofylline and oxpentifylline on motor activity is probably due to their low brain penetration ratio or low adenosine A1 affinity in comparison with theophylline. The decrease in the motor activity by MPX may be, in part, mediated by cAMP or adenosine.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1995

Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats.

Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the beta-lactam antibiotic cefpiramide (CPM), which is mainly excreted into bile, were investigated in 10- and 20-week-old EHBRs and were compared with those in 20-week-old healthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SDRs, significant decreases (by approximately 30%) in the systemic clearance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion.

Aging↗

PubMed1995

Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin.

The effects of single coadministrations of one of three traditional Chinese medicines, Hotyu-ekki-to, Rikkunshi-to, and Juzen-taiho-to, on the pharmacokinetics of levofloxacin (LVFX) were investigated with eight healthy volunteers in an open, random crossover fashion. Subjects each received a single oral dose of LVFX (200 mg) alone and then with a single coadministration of each Chinese medicine. There were no significant differences in any pharmacokinetic parameters of LVFX between the groups. Also, no significant changes in the urinary recovery (> 80%) and renal clearance of LVFX were observed. These results indicate that the Chinese medicines tested have no significant effect on the rate and extent of bioavailability or renal excretion of LVFX.

Adult↗

PubMed1995

Influence of a newly developed quinolone, T-3761, on pharmacokinetics of theophylline in rats.

The effect of a new quinolone, T-3761, on the pharmacokinetics and metabolism of theophylline was investigated with rats. T-3761 at a high dose (20 mg/kg of body weight) was injected intravenously 10 min before an intravenous administration of theophylline (10 mg/kg). The presence of T-3761 slightly delayed the disappearance of theophylline from plasma. Parameters related to the pharmacokinetic interaction between theophylline and T-3761 were estimated by noncompartmental methods. A significant decrease (approximately 25%) in the systemic clearance of theophylline was observed in the presence of T-3761. However, no significant changes between the control group and the T-3761-treated groups in the volume of distribution at a steady state were observed. Pretreatment with T-3761 increased the urinary excretion of unchanged theophylline (by approximately 25%) and decreased the nonrenal clearances (by approximately 30%), indicating that T-3761 inhibits the metabolism of theophylline. These findings suggest that T-3761 at the dose used in this study affects the pharmacokinetics and metabolism of theophylline.

4-Quinolones↗

PubMed1995

Time-dependent changes in the pharmacokinetics and renal excretion of xanthine derivative enprofylline induced by bacterial endotoxin in rats.

Time-dependent changes in the pharmacokinetics and renal handling of enprofylline induced by bacterial endotoxin (Klebsiella pneumoniae LPS) were investigated in rats. To evaluate the early effect of LPS on kidney functions and the renal excretion of enprofylline, which is an organic anion drug excreted primarily by an active tubular secretion, LPS (250 micrograms/kg) was infused for 5 min under constant infusion at rates of 2.3 and 23 micrograms/min/kg for inulin and enprofylline, respectively. LPS caused a drop in the glomerular filtration rate (GFR), estimated as the renal clearance of inulin, to 65-75% of that observed in the control rats within 30 min after the LPS treatment. The renal clearance (CLr) of enprofylline decreased in conjunction with GFR, while the percentage of decrease in the CLr was slightly greater than that in GFR. LPS-induced decreases in the CLr for enprofylline and GFR continued over the testing period of 120 min. The time-dependent effect of LPS on the pharmacokinetics of enprofylline was examined by a single injection of enprofylline (2.5 mg/kg) to rats pretreated 2, 10 or 24 h earlier with or without LPS. The pharmacokinetic parameters of enprofylline were determined by a model-independent method. Significant changes in the systemic clearance for enprofylline were observed in rats pretreated 2 and 10 h earlier with LPS, but no such changes were observed in rats pretreated 24 h earlier with LPS. These findings indicate the existence of a time-dependent effect of LPS on the pharmacokinetics of enprofylline, and suggest that LPS at a dose of 250 micrograms/kg, at least, does not induce cytotoxicity to kidney cells.

Animals↗

PubMed1995

[Nerve growth factor strategy and preparation of animal model for Alzheimer-type senile dementia].

Nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system. In senile dementia of the Alzheimer type (SDAT), learning and memory are impaired by the loss of neurons in the magnocellular cholinergic neuronal system. It is, therefore, of interest to investigate the role of NGF in this degenerative disorder. Since NGF does not cross the blood-brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We tried to develop drugs which could be taken orally and stimulate the NGF synthesis in the brain. In addition, we attempted to develop a SDAT animal model using osmotic minipump to infuse beta-amyloid protein into cerebral ventricle, since there are no SDAT model animals accompanied with various pathophysiological changes. We demonstrate here that the oral administration of propentofylline, idebenone and trimethylquinone derivative, potent in vitro NGF synthesis stimulators, induced the increase in NGF protein and mRNA, and in choline acetyltransferase activity, in basal forebrain-lesioned and aged rats, but not in intact young rats. These drugs also ameliorated the behavioral deficits in habituation, water maze, and passive avoidance tasks in these animals. These results suggest that these drugs stimulated NGF synthesis in vivo and ameliorated the behavioral deficits which were accompanied with the reduced choline acetyltransferase activity in the basal forebrain-lesioned and aged rats. In terms of the SDAT animal model, the performance of the water maze and passive avoidance tasks was impaired and choline acetyltransferase activity significantly decreased in beta-amyloid protein-treated rats. Histochemical results showed the deposition of beta-amyloid protein in the cortex and hippocampus and atrophy and loss of hippocampal neurons. These results suggest that the deposition of beta-amyloid protein in the brain is related to the impairment of learning and cholinergic neuronal degeneration, and that beta-amyloid protein-treated rats could be an animal model for SDAT and used for the screening of drugs for SDAT.

Alzheimer Disease↗

PubMed1995

[Trial to produce animal model of Alzheimer's disease by continuous infusion of beta-amyloid protein into the rat cerebral ventricle].

To develop an animal model of Alzheimer's disease, we investigated the toxicity of beta-amyloid protein which is a component of senile plaques in Alzheimer's disease. beta-Amyloid was infused into the cerebral ventricle of rats for 14 days using a mini-osmotic pump. The performance of habituation, water maze and passive avoidance tasks in beta-amyloid protein-treated rats was impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after cessation of the infusion. However, the learning impairment is recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Further, beta-amyloid protein altered the staining of nuclei of cells in the hippocampus only 2 weeks after cessation. These results suggest that beta-amyloid protein damages the central nervous system in vivo, and that this animal could be used as a model of Alzheimer's disease.

Aging↗

PubMed1994

SKF-10,047 reverses stress-induced motor suppression: interaction with dopaminergic system.

Mice exhibited a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. This stress-induced motor suppression was dose dependently attenuated by (+/-)-SKF-10,047, a sigma receptor agonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the sigma receptor ligands (+)-pentazocine and 1,3-di-(2-tolyl)guanidine. This effect of (+/-)-SKF-10,047 was antagonized by BMY-14802, a sigma receptor antagonist, and by pimozide, a dopamine receptor antagonist. When dopaminergic neurons were destroyed by pretreatment with 6-hydroxydopamine, the effect of (+/-)-SKF-10,047 on the stress response was also attenuated. Furthermore, (+/-)-SKF-10,047 dose dependently reversed the decrease in striatal dopamine turnover in the conditioned suppression group. These results suggest that stress-induced motor suppression is restored by (+/-)-SKF-10,047 acting through sigma receptors, which are closely linked to the dopaminergic neuronal system.

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