Asymmetric alpha-substituted phenethylamines. VI. Synthesis and analgesic activity of optically pure (R)- and (S)-N-alkyl-1-cyclohexyl-2-phenylethylamines.
Explore the source record for details and available documents.
Analgesics↗
Biomedical subjects
T Yoshii
Publications and source records attributed to T Yoshii.
Avidity effect on the interaction between Helix pomatia A hemagglutinin and N-acetylgalactosamine-conjugated dextran.
Explore the source record for details and available documents.
Acetylgalactosamine↗
[Reversible reactivity of the dansyl derivative of N-acetylgalactosamine with Helix pomatia A hemagglutinin].
Explore the source record for details and available documents.
Acetylgalactosamine↗
[Fluorometric investigation of anti-methamphetamine antibody-hapten reactions].
Explore the source record for details and available documents.
Amphetamine↗
[Sex differences in the physical dependence on barbital in rats].
Sex differences in physical dependence on barbital (BAR), which is not readily metabolized in rats, were studied by the drug-admixed food method. The concentration of BAR in the food was gradually increased from 1 and 2 up to 6 and 8 mg/g food concurrently available to each rat over a period of 36 days in both male and female Sprague-Dawley rats. Sedation and muscle relaxation were observed in males at the 4 and 6 mg/g condition and to a greater degree at 6 and 8 mg/g of food. This effect was seen only at the highest drug concentration, 6 and 8 mg/g food, in females. Physical dependence was assessed in both sexes after substitution of normal food for the BAR-admixed food. Various signs of BAR withdrawal were observed including vocalization, irritability, muscle rigidity, tremors and convulsions. The incidence of convulsions was 76.9% in females and 45.5% in males, respectively. Maximum weight loss was 15.4% in females and 12.1% in males. However, brain BAR concentrations in the male rats were higher than that in the female rats 9 hours before onset of withdrawal and at all later time points tested. Thus, we have demonstrated that weak sex differences in physical dependence on BAR exist and suggest that this difference resulted from a difference in CNS sensitivity to BAR.
Animals↗
[Rapid diagnosis of herpes simplex viruses by the fluorescent antibody test using monoclonal antibodies].
Explore the source record for details and available documents.
Adult↗
[Chronopharmacological study of physical dependence on morphine in rats].
Relationship between withdrawal time or naloxone injection time and withdrawal signs were examined in morphine-treated rats. Sixty-five rats were treated chronically with morphine-admixed food (1 mg/g food) for 7 days and were divided into 13 groups. The rats of 4 groups were abruptly withdrawn from morphine, and the rats of another 4 groups were given naloxone (3 mg/kg, s.c.) at 20:00 on the 8 th day and 2:00, 8:00 and 14:00 on the 9 th day after the morphine administration, respectively. Withdrawal signs were observed at intervals of 2 hr. After each naloxone injection, abnormal behaviors were observed for 60 min, and body weight was measured for 3 hr at intervals of 15 or 30 min. In the withdrawal test, weight loss at 24 hr after withdrawal in each group was approximately 10%, and there was no difference between each group. However, the body weight of non-treated rats and morphine-treated rats increased during the night period (20:00-8:00) and decreased during the daytime (8:00-20:00). Therefore, body weight reached the minimum at 20:00, and then this time is appropriated for withdrawal. In the naloxone test, withdrawal signs in the night period were more potent than that in the daytime. The withdrawal signs induced by naloxone at 8:00 showed the maximum magnitude. Plasma morphine levels in rats treated with morphine-admixed food were high in the night period and low in the daytime. These results suggest that the magnitude of naloxone-precipitated withdrawal signs depends on the amount of morphine in the plasma.
Animals↗
Sex differences in the induction of physical dependence on pentobarbital in the rat.
Sex differences in physical dependence on sodium pentobarbital in the rat were studied by the drug-admixed food (DAF) method. With male rats, the concentration of pentobarbital in the food was gradually increased from 2 to 30 mg/g over a period of 50 days. The final level of drug intake was approximately 1.7 g/kg/day. At pentobarbital concentrations of 20 and 22 mg/g of food, sedation and mild muscle relaxation were observed. At the highest drug concentration, 30 mg/g of food, marked muscle relaxation was noted. With female rats, the concentration of pentobarbital in the food was gradually increased from 1 to 16 mg/g over a period of 47 days. The final level of intake was approximately 1.0 mg/kg/day. At drug concentrations of 12 and 14 mg/g, sedation and mild muscle relaxation appeared. At 16 mg/g, female rats showed marked muscle relaxation similar to that of the male rats. To produce severe loss of muscle tone, the male rats required twice as much pentobarbital as the female rats. After substitution of normal food for the pentobarbital-admixed food, various signs of pentobarbital withdrawal occurred in both sexes. These signs included vocalization, irritability, muscle rigidity, tremors and convulsions. Onset of withdrawal was more rapid in the females, and the maximum weight loss was greater, 8.0% compared to 3.8% in the males. Physical dependence on pentobarbital was easily developed in both sexes by the DAF method. There was a marked sex difference in withdrawal which we attribute to sex differences in drug metabolizing enzyme activity.
Animals↗
Genome type analysis of adenovirus type 4 isolates, recently obtained from clinically different syndromes in some areas in Japan.
DNA cleavage analyses with EcoRI, HindIII and BamHI were carried out to investigate genome types of recent Ad 4 isolates obtained from acute respiratory disease (8 strains), and ocular disease (11 strains) in Japan. DNA cleavage patterns of all 19 isolates studied were identical regardless of whether they were recovered from respiratory tract or conjunctiva, but were distinct from that of the prototype strain.
Adenoviridae Infections↗
Induction of physical dependence on morphine in mice by the drug-admixed food method.
The drug-admixed food method was applied to ICR strain mice for studying development of physical dependence on morphine. Mice were treated with morphine-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. During the treatment, the mice did not show any signs of toxicity. Plasma and brain morphine levels were quantitatively related to the morphine concentration in drug-admixed food. The plasma morphine level showed a circadian rhythm, and the level was higher than 0.15 microgram/ml throughout the day. The morphine-treated mice manifested body weight loss, diarrhea and ptosis from 4 hr after morphine withdrawal and showed maximum body weight loss at 12 hr. In the naloxone-precipitated test, jumping and body shakes were observed in mice treated with morphine-admixed food (2 mg/g food) at least for 1 day. Moreover, in mice treated with morphine (2 mg/g food) for 3 days, marked jumping and body shakes and some writhing were observed after naloxone administration. These results suggest that the drug-admixed food method has advantages of easily and rapidly inducing the physical dependence on morphine in mice without causing toxicity and death.
Animal Feed↗
Induction of physical dependence on codeine in the rat by drug-admixed food ingestion.
The developmental process of physical dependence on codeine has been explored in rats treated with codeine-admixed food (0.5 mg/g food) during 1 to 7 days. In rats treated with codeine for more than 2 days, body weight loss was markedly observed after the abrupt codeine withdrawal. The intensity and time course of body weight loss increased according to the duration of codeine treatment. After the codeine withdrawal, behavioral signs such as diarrhea, ptosis and vocalization were observed. In the naloxone-precipitated withdrawal test, rats treated with codeine for 1 day manifested a loss of body weight after naloxone challenge, and the intensity of body weight loss increased according to the duration of codeine treatment. After naloxone injection, the codeine-treated rats showed abnormal behaviors such as diarrhea, ptosis, teeth chattering , salivation, body shakes, vocalization, nose bleed, irritability, lacrimation and writhing. The total score, evaluated by the ranking system for precipitated withdrawal behaviors, was correlated with the duration of codeine treatment. These results suggest that naloxone-precipitated withdrawal signs are powerful in comparison with that after codeine withdrawal, and the weight loss is a common index for quantitative assessment of physical dependence on narcotics in the natural and naloxone-precipitated withdrawal tests. It is concluded that the drug-admixed food ingestion method has the advantage of rapidly inducing a high degree of physical dependence on codeine.
Animals↗
[Assessment of morphine-type physical dependence liability in mice using the drug-admixed food method].
Physical dependence on morphine-type drugs (morphine, codeine and pethidine) in mice were examined by the drug-admixed food method. Mice were treated with drug-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. Morphine- and codeine-treated mice showed withdrawal signs when they were given naloxone (5 mg/kg, s.c.), while pethidine-treated mice did not show the withdrawal signs. However, mice treated with pethidine-admixed food (1-6 mg/g food) for 28 days showed naloxone precipitated withdrawal signs. Thus, the data obtained with mice indicate that pethidine produces a weak physical dependence. On the other hand, codeine (40 mg/kg, s.c.) and pethidine (100 mg/kg, s.c.) administration suppressed the abrupt withdrawal signs of morphine-dependent mice that were treated with morphine-admixed food, while the withdrawal signs were completely suppressed in mice administered only 5 mg/kg morphine. These results suggest that the physical dependence liability of morphine type drugs can be predicted by the drug-admixed food method.
Administration, Oral↗
[Comparison of three methods of inducing physical dependence to morphine in rats using short-term medication].
A comparison of several methods for developing physical dependence to morphine was made. Male Sprague-Dawley rats were treated with morphine-admixed food (drug-admixed food, DAF; 0.5 and 1 mg/g food), morphine slow release emulsion (SRE; 75, 100 and 150 mg/kg) and morphine (75 mg) pellets. In the SRE and pellet methods, the typical signs of morphine toxicity, such as catatonia, exophthalmos and shallow respiratory movements, were observed 15-20 min after the treatment and these signs were maintained for 14-18 hr. In rats treated with SRE and pellets, plasma morphine levels reached a maximum 1 day after the morphine treatment, and subsequently decreased, while plasma morphine levels in rats treated with DAF increased treatment period-dependently. Withdrawal signs precipitated by naloxone (3 mg/kg, sc) in rats treated with DAF, SRE and pellets were characterized by loss of body weight, shaking, vocalization, diarrhea, ptosis, tooth-chattering, nose bleed, salivation and lacrimation. Naloxone-precipitated withdrawal signs reached a maximum 1-2 days after treatment with SRE and pellets, and were correlated with the duration of DAF treatment. Rats treated with DAF, SRE (150 and 225 mg/kg) and pellets for 3 days, manifested loss of body weight, diarrhea etc. after the morphine withdrawal. Maximum body weight loss in each group was 7-10% at 1-2 days after the morphine withdrawal. It was thus, concluded that physical dependence on morphine can be induced rapidly by these three methods. However, the SRE and pellet methods induced morphine toxicity and it was difficult to maintain physical dependence on morphine in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Motility effects of methamphetamine in morphine-tolerant mice by the DAP method].
We reported that the reverse tolerance to the effect of morphine on ambulatory activity did not develop in mice treated with morphine-admixed food. In this study, effects of repeated administration of methamphetamine on ambulatory activity were studied in mice treated with morphine-admixed food. The ambulatory activity was determined by the tilting cage method. Methamphetamine injection (1 mg/kg, s.c.) was repeated at 3 approximately 4 day intervals. The ambulatory activity was enhanced progressively when methamphetamine was repeatedly given in mice. However, the enhancing effect was not observed in mice treated with morphine-admixed food (1 mg/g food). Moreover, in a single injection experiment, the effect of the combination of methamphetamine and morphine on ambulatory activity was more potent than that of each drug. These results suggested that the reverse tolerance to methamphetamine did not develop under the condition of exposure to morphine by the DAF (drug-admixed food) method, and the developmental mechanism of reverse tolerance to methamphetamine might be similar to that of morphine.
Administration, Oral↗
Thermodynamics of binding between saccharides and Helix pomatia A hemagglutinin.
Binding constants for the interactions between Helix pomatia A hemagglutinin and the following saccharides were estimated at pH 7.0 and 25 degree C, using the circular dichroism method: N-acetyl-D-galactosamine, 5700 M-1; N-acetyl-D-glucosamine, 1000 M-1; melibiose, 86 M-1; raffinose, 350 M-1. The binding of N-acetyl-D-galactosamine to Helix pomatia A hemagglutinin was investigated in detail, using the circular dichroism and fluorescence methods, over the temperature range 5-50 degree C and pH range 7.0-2.5. The thermodynamic parameters, delta H degree (kcal . mol-1), delta G degree (kcal . mol-1), and delta S degree (e.u.), for this binding reaction at 25 degrees C were estimated as follows: -11.3, -5.24, -20.3 at pH 7.0; -9.1, -5.71, -11.2 at pH 4.5; -38.3, -3.19, -118 at pH 2.5. The negative values of delta H degrees and delta S degrees at pH 2.5 were especially large. This may be related to the restoration of the Helix pomatia A hemagglutinin molecule or its binding site from an unstable configuration caused by lowering the pH of the reaction medium to the original configuration of the presence of N-acetyl-D-galactosamine.
Animals↗
Development of physical dependence on and tolerance to morphine in rats treated with morphine-admixed food.
1. The development process of physical dependence on and tolerance to morphine has been explored in rats treated with morphine-admixed food (0.5 mg/g of food) during 1 to 7 days. 2. In the morphine-treated animals, body weight loss was observed after the abrupt morphine withdrawal. 3. Intensity and time course of the weight loss were correlated to the morphine treatment. 4. On the other hand, the morphine-treated rats showed abnormal behaviors, such as diarrhea, ptosis, teeth chattering, salivation, body shakes, vocalization, nose bleed, irritability, aggression, lacrimation and writhing upon naloxone injection. 5. Loss of body weight, measured 3 hours after naloxone injection, was also correlated to the duration of morphine treatment. 6. Tolerance to the analgesic effect of morphine developed within one day in rats treated with morphine-admixed food. 7. The drug-admixed food ingestion method has the advantage of rapidly inducing a high degree of physical dependence and tolerance without causing morbidity or lethality in animals. It also eliminates the need for excessive handling of animals.
Animals↗
Cardiovascular responses to sustained isometric arm flexion and knee extension at 10, 20, 30, 40 and 50% MVC.
Explore the source record for details and available documents.
Adolescent↗
[Motility effects of morphine in morphine-tolerant mice by the DAF method].
Effects of repeated administration of morphine on ambulatory activity were studied in mice treated with morphine-admixed food. The ambulatory activity was determined by the tilting cage method. Morphine injection (10 mg/kg s.c.) was repeated at 3-4 day intervals. The ambulatory activity was enhanced progressively when morphine was repeatedly given to mice. However, the enhancing effect was not observed in mice treated with morphine-admixed food (1 mg/g food). These results suggested that the reverse tolerance to morphine did not develop under the condition of exposure to morphine by DAF (drug-admixed food) method. In case of treatment with morphine-admixed food of increasing concentration (1,2 and 3 mg/g food), the ambulatory activity of morphine was decreased. According to the studies done so far, tolerance development to the stimulant effects was not observed. This study demonstrates that the tolerance develops to the stimulant effects of morphine on the schedule of treatment with morphine of increasing doses by the DAF method.
Administration, Oral↗