Influence of adrenergic nervous and prostaglandin systems on hydralazine-induced renin release

The role of the beta-adrenergic nervous and prostaglandin systems in vasodilator-induced activation of the renin-angiotensin system was studied in conscious rats. The plasma renin activity (PRA) response to intravenous hydralazine (0.25, 0.5 and 1 mg/kg body wt.) was compared to the PRA response following administration of similar doses of hydralazine to rats pretreated with either indomethacin (3 mg/kg body wt. i.v.) or indomethacin and propranolol (1 mg/kg body wt. i.v.). PRA increased significantly above control levels after each of the hydralazine doses. In rats pretreated with indomethacin, PRA did not increase with the 0.25 mg/kg dose of hydralazine; increased significantly with the 0.5 mg/kg dose but remained significantly lower than the PRA response in the absence of indomethacin; and increased with the 1 mg/kg dose to a level not significantly different from PRA in rats receiving only hydralazine. When rats were pretreated with indomethacin and propranolol, PRA did not increase significantly in response to either the 0.25 or 0.5 mg/kg doses of hydralazine. Although a statistically significant increase in PRA was noted with the 1 mg/kg dose of hydralazine, the level of PRA achieved was very low and only 15% of that observed with the other two treatment regimens (i.e., hydralazine alone or indomethacin and hydralazine). These results demonstrate that vasodilator-induced renin release is only partially mediated via the prostaglandin system, that the degree of this control is related to the intensity of vasodilator stimulus and that renin release following administration of hydralazine can be attributed almost entirely to activation of the beta-adrenergic nervous and prostaglandin systems.     

The influence of pre-anaesthetic administration of buprenorphine on the anaesthetic effects of ketamine/medetomidine and pentobarbitone in rats and the consequences of repeated anaesthesia

Rats received pentobarbitone (60, 48 and 36 mg/kg i.p.) or ketamine/medetomidine (75/100, 60/80 and 45/60 mg/microg/kg i.p.) alone, or one hour following buprenorphine (0.5 mg/kg s.c.). Animals were anaesthetized once per week for 6 weeks with one of three anaesthetic doses according to a randomized block design. In the pentobarbitone group, animals which received buprenorphine had longer sleep times (236 +/- 22 cf. 204 +/- 21 min) and longer durations of surgical anaesthesia (83 +/- 14 cf. 27 +/- 8 min) (P<0.01), these effects being potentiated with increasing anaesthetic doses (P<0.01). A greater degree of respiratory depression was found in animals that received buprenorphine (P<0.01) although this was judged clinically acceptable in all cases. Unexpectedly high mortality and a high incidence of anaesthetic complications (nine of 16 animals) in the ketamine/medetomidine group made statistical analysis of these data impossible. We conclude that for pentobarbitone, pre-anaesthetic administration of buprenorphine reduces the dose of anaesthetic required to produce surgical anaesthesia, in addition to the presumed benefits of pre-emptive analgesia. In view of the high mortality encountered, we advise caution when considering pre-anaesthetic use of opioids in combination with ketamine/medetomidine in rats.     

Antihypertensive substance in seeds of Areca catechu L

Among various tannins tested, Areca II-5-C, a fraction isolated from seeds of Areca catechu L., showed the most potent angiotensin-converting enzyme (ACE) inhibitory activity in vitro. Its antihypertensive activity was therefore investigated in normotensive and spontaneous hypertensive rats (SHR) after both oral and intravenous (i.v.) administration. The activity was compared with that of captopril (D-3-mercapto-2-methylpropanoyl-L-proline), a potent ACE inhibitor. Oral administration of Areca II-5-C to SHR produced a lasting, dose-related antihypertensive effect, and the responses obtained with doses of 100 and 200 mg/kg were comparable to those of captopril at doses of 30 and 100 mg/kg. Intravenous administration of Areca II-5-C to SHR produced a rapid and marked reduction in blood pressure at doses of 10 and 15 mg/kg. The maximum antihypertensive effect of Areca II-5-C in SHR, at an i.v. dose of 15 mg/kg, was about 5 times as large as that of captopril at the same dose. Although the vasopressor response to norepinephrine and vasodepressor responses to bradykinin and acetylcholine were not appreciably changed by i.v. treatment with Areca II-5-C at a dose of 5 mg/kg, it did produce dose-related inhibition of the pressor responses to angiotensin I and II. It is suggested that Areca II-5-C has favorable properties as a hypotensive drug through its ability to inhibit the pressor responses to both angiotensin I and II.     

Morphine inhibits TRH-induced gastric contractile activity.

This study investigated the effect of centrally and peripherally administered thyrotropin releasing hormone (TRH) on gastric contractile activity of rats 14, 21, 28 and adult (greater than or equal to 50) days (D) of age, and the effect of morphine pretreatment on that response. Rats were anesthetized with urethane, then a tension transducer was implanted on the anterior gastric corpus. Following baseline recording, rats were pretreated with intraperitoneal morphine (2 mg/kg). TRH (5 micrograms) in saline or saline alone (0.6 microliters) was then injected into the cisternum magnum. Additionally, dose response to TRH was examined in 14- and 50-day-old rats. Intracisternal TRH induced a dose-related increase in gastric contractile activity in both 14- and 50-day-old rats. Higher doses of TRH (10 and 30 micrograms) prolonged the response as compared to low doses. Peripheral morphine pretreatment blocked the TRH-induced increase in gastric contractile activity in all age groups although a higher morphine dose (10 mg/kg) was needed to block the effect in 28D rats. Intravenous TRH (5, 10, 30 micrograms) produced an increase in gastric contractile activity in 14D rats which was blocked by vagotomy.     

Efficacy of human serum butyrylcholinesterase against sarin vapor

Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD(50) challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure to OP nerve agents on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. Male G?ttingen minipigs were subjected to one of the following treatments: (1) air exposure; (2) GB vapor exposure; (3) pretreatment with 3 mg/kg of Hu BChE followed by GB vapor exposure; (4) pretreatment with 6.5 mg/kg of Hu BChE followed by GB vapor exposure; (5) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m(3) for 60 min, a dose lethal to 99% of untreated exposed pigs (LCt99). EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period, was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. All animals exposed to GB vapor alone or pretreated with 3 or 6.5 mg/kg of Hu BChE, died following exposure to GB vapor. All five animals pretreated with 7.5 mg/kg of Hu BChE survived the GB exposure. The amount of GB bound in plasma was 200-fold higher compared to that from plasma of pigs that did not receive Hu BChE, suggesting that Hu BChE was effective in scavenging GB in blood. Additionally, pretreatment with 7.5 mg/kg of Hu BChE prevented cardiac abnormalities and seizure activity observed in untreated animals and those treated with lower doses of Hu BChE.     

Effects of paraquat on anti-oxidant system in rats

The toxic effects of paraquat on the anti-oxidant defense system of male albino rats were evaluated, after administering either a single dose (1.5 and 7.5 mg/kg of body weight) or continuous daily doses (same as above, i.e., 1.5 mg/kg and 7.5 mg/kg of body weight) for 3 and 7 days. Glutathione levels in blood cells, liver, lung and kidney tissues decreased in a dose and time dependent manner. Glutathione reductase and glucose-6-phosphate dehydrogenase activity decreased, whereas the activity of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase increased in paraquat exposure. Malondialdehyde formation also increased in a dose and time dependent manner. The alterations of anti-oxidant system particularly glutathione can be utilized as biomarkers during management of paraquat poisoning.     

Effect of praseodymium chloride on liver microsomal enzymes of rats

A single i.v. dose (5 mg/kg) of a light lanthanon, praseodymium, prolonged the duration of hexobarbital-induced sleep and zoxazolamine-induced paralysis, as well as it modified pharmacokinetic parameters of hexobarbital and zoxazolamine, in rats. Half-lives (t1/2) and area under the curve (AUC) were increased, while elimination coefficient (beta) and clearance (Cl) were decreased. However, in daily doses of 1 mg/kg i.p. for 15 days, praseodymium did not alter pharmacological effects and pharmacokinetic parameters. The in vitro hydroxylation of hexobarbital and zoxazolamine by liver microsomes was inhibited when the animals were treated previously with a single i.v. dose (5 mg/kg) of praseodymium chloride. In these animals, the amount of cytochromes P-450 and b5 were reduced significantly, whereas that of NADPH-cytochrome c reductase remained unchanged. The pretreatment of animals with phenobarbital normalized the microsomal enzyme impairment caused by praseodymium.     

Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats

Withania somnifera (WS) or its psychotropic preparation is known to play a critical role in morphine, alcohol and benzodiazepines addiction. This study investigates the role of WS in acute ethanol and withdrawal from chronic ethanol consumption using elevated plus maze paradigm in rats. Acute administration of ethanol (1.5-2 g/kg, ip) triggered anxiolytic effect and withdrawal from prolonged ethanol (9% v/v ethanol, 15 days) consumption elicited enhanced behavioral despair (anxiety). Acute administration of WS (50 mg/kg, oral) potentiated the anxiolytic action of subeffective dose of ethanol (0.5 or 1 g/kg, ip). Moreover, the ethanol withdrawal anxiety was markedly antagonized in dose dependent manner by WS at 200 and 500 mg/kg or higher dose of ethanol (2.5 g/kg). However, co-administration of subeffective doses of WS (50 mg/kg, oral) and ethanol also attenuated withdrawal-induced anxiety due to chronic ethanol (9% v/v ethanol, 15 days) consumption. The results suggest the protective effect of WS in the management of ethanol withdrawal reactions.     

Intravenous morphine infusion (IMF) to drug-naive, conscious rats evokes bradycardic, hypotensive effects, but pressor actions are elicited after IMF to rats previously given morphine

Hemodynamic (blood pressure and heart rate) responses of conscious drug-naive rats were studied following intravenous (i.v.) infusion of sterile saline, morphine sulphate, and then naloxone hydrochloride, as well as of other groups previously injected with morphine sulphate. Those groups chronically given morphine sulphate received twice daily injections of morphine sulphate (5 mg/kg, s.c. per injection) for 3 or 6 days before testing with the i.v. infusion of morphine sulphate. Drugs were infused (135 microL/min) through an indwelling femoral venous catheter via a Harvard infusion pump, and blood pressure was recorded from the abdominal aorta via a femoral arterial catheter. Other pretreatment studies were done to determine the receptor mechanisms mediating the blood pressure responses of drug-naive and chronic morphine-treated rats, whereby equimolar doses (0.32 mumol) of specific receptor antagonists were given as a bolus i.v. injection 5 min after saline but before subsequent infusion with morphine sulphate. Intravenous infusion of morphine sulphate (7.5 mg/kg total over 15 min) to drug-native rats caused a transient but precipitous fall in mean arterial pressure and mean heart rate with an associated rise in mean pulse pressure; these effects were blocked in other groups pretreated with atropine. Interestingly, however, rats chronically injected with morphine sulphate for 3 days previously evoked a transient pressor response when subsequently infused i.v. with morphine sulphate, actions that were blocked in other groups when pretreated i.v. with 0.32 mumol of phentolamine, yohimbine, prazosin, or guanethidine. A greater and persistent pressor response occurred following morphine infusion to groups of rats previously injected over 6 days with morphine sulphate, which was associated with tachycardia during the later stages of the 15-min morphine sulphate infusion period. The prolonged pressor and tachycardic responses of this 6-day chronically injected group were completely blocked in another group pretreated i.v. with both phentolamine and propranolol (0.32 mumol). The results suggest that morphine sulphate infusion to conscious, drug-naive rats evokes classical hypotensive effects due to decreases in mean heart rate caused by activation of parasympathetic vagal activity. With 3 or 6 days of chronic morphine sulphate administration beforehand, subsequent i.v. infusion of morphine sulphate evoked pressor actions felt to be caused by a progressive activation of the sympathetic nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)     

The L-DOPA-sparing effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP] in reserpine-pretreated rats

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP], a highly potent enhancer of impulse propagation-mediated release of catecholamines and serotonin in the brain, and significantly increased the locomotor activity of normal rats at the doses of 0.3 and 1 mg/kg s.c. (P < 0.05), while L-DOPA (200 and 400 mg/kg i.p.) had no significant effect. The locomotor activity of rats simultaneously administered L-DOPA and (-)-BPAP was significantly higher than with (-)-BPAP alone (P < 0.05). In rats pretreated with reserpine (1 mg/kg i.v.), the hypolocomotion was significantly reversed by 400 mg/kg i.p. L-DOPA, or 1 or 3 mg/kg s.c. (-)-BPAP (P < 0.05). Furthermore, the combined administration of subthreshold doses of 200 mg/kg i.p. L-DOPA and 0.3 mg/kg s.c. (-)-BPAP highly potentiated the locomotor activity in the reserpine-pretreated rats. However, (-)-BPAP failed to reverse the hypolocomotion in rats pretreated with reserpine + alpha-methyl-DL-p-tyrosine. Thus, (-)-BPAP was demonstrated to possess the L-DOPA-sparing effect in normal and reserpine-pretreated rats.     

Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat

Pharmacological activation of the glucagon-like peptide-1 (GLP-1) receptor and inhibition of the cannabinoid CB1 receptor were found to reduce food intake and body weight in humans and animals. Since earlier studies revealed that endocannabinoids may interact with other neurotransmitters to affect feeding behavior, we have examined whether a stable GLP-1 agonist, exendin-4 and a CB1 receptor antagonist, AM 251, may reciprocally enhance their inhibitory effects on food consumption in the rat. Additionally, we have tested whether the blockade of the GLP-1 receptor by exendin (9-39) modifies AM 251-dependent effects on energy balance. In a dose-response study, male Wistar rats were injected intraperitoneally with either 1.5-6.0 μg/kg exendin-4, 0.5-2 mg/kg AM 251, 80-320 μg/kg exendin (9-39) or their vehicle and the daily food and water intake as well as body weight changes were monitored two days before and two days after the injection. Exendin-4 at a dose of 3.0 and 6.0 μg/kg and AM 251 at a dose 2 mg/kg decreased significantly 24-hour food intake and body weight. Therefore, in the next study, the effects of lower doses of exendin-4 (1.5 μg/kg) and AM 251 (1.0 mg/kg) administered alone or together on food consumption were compared. As opposed to being injected alone, the co-administration of the two resulted in a marked decrease in both daily food intake and body weight. Exendin (9-39) did not modify the suppressory effect of the highest AM 251 dose on food consumption. Apparently, the effect of AM 251 on the appetite is not mediated by GLP-1. The concomitant stimulation of GLP-1 receptor and blockade of CB1 receptor, however, may act synergistically to inhibit appetite in the rat.     

有机磷杀虫剂——灭克磷对丛枝菌根真菌Glomus mosseae生长的效应

采用多室隔网培养法,在宿主植物生长状况相同的条件下研究了土壤中不同浓度灭克磷对AM真菌生长的直接效应。与对照相比,0.5、1.5和3.5mg/kg灭克磷使Glomusmosseae菌丝生长量和具有琥珀酸脱氢酶活性的菌丝生长量明显地增加;随着灭克磷剂量的增加,菌丝总量的相对生长速率呈降低趋势,但在数值上仍然高于对照的;与此同时,高剂量(1.5和3.5mg/kg)灭克磷使Glomusmosseae活性菌丝量的相对增长速率明显低于对照,达到几乎停止的水平。上述结果说明,低剂量灭克磷(0.5mg/kg)对AM真菌生长和代谢活性都有一定刺激作用,但是在高剂量灭克磷(1.5和3.5mg/kg)下菌丝生物量的增加和周转速度的加快只是AM真菌对毒物的应激反应。     

Prolactin (PRL) release-inhibiting properties of the alpha 2 adrenergic receptor antagonist idazoxan: comparison with yohimbine

The effects of the alpha 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secretion of PRL were compared in nonanesthetized male rats bearing permanent intraatrial cannulae for i.v. drug delivery and serial blood sampling. YOH induced a dose-related elevation of basal plasma PRL levels. ID had either no effect or a tendency to lower them and effectively inhibited stimulation of PRL secretion with morphine, 5-hydroxytryptophan (5HTP), quipazine or restraint stress. YOH at low doses did not alter the PRL secretory responses to these stimuli or enhanced them at the highest dose used (1.56 mg/kg). ID inhibited the PRL-stimulating, effect of 5HTP or morphine following inhibition of NE synthesis with FLA63 or pretreatment with clonidine. It also blocked the effect of quipazine in rats pretreated with prazosin. It is concluded that ID, in a complete contrast to YOH effectively inhibits PRL secretion. The inhibitory mechanism appears to be unrelated to its interaction with the alpha adrenergic receptors.     

Effect of multiple dosing on the analgesic action of diflunisal in rats

This investigation was designed to compare the analgesic effect of the initial dose of a repetitively dosed non-narcotic analgesic with the analgesic effect of a subsequent dose given 3 days later. To exclude gradual drug accumulation as a variable, the first ("loading") dose was larger than the maintenance doses. Male Sprague-Dawley rats received 100 mg/kg diflunisal i.v. as the first dose and 70 or 75 mg/kg every 12 hours thereafter. The analgesic effect of the first and seventh doses was determined as the pain threshold (voltage) upon electrical stimulation of the tail every 15 to 30 minutes from the third to the ninth hour after dosing. Blood samples for drug assay were obtained at 3 and 9 hours. A control group received injections of solvent for 6 doses and 100 mg/kg diflunisal as the seventh dose. There were no statistically significant differences between the area under the total or free (unbound) drug concentration versus time curves of the first and seventh dose but the average analgesic effect (area under the voltage increase versus time) of the seventh dose was only 28 percent that of the first dose. The areas under the drug concentration and analgesic effect versus time curves of the diflunisal dose given as the seventh injection to the control rats were similar to those produced by the first dose given to the multiple dosed rats. The results of this investigation show that the analgesic effect of a non-narcotic drug decreases substantially during repeated dosing in an animal model of experimental pain. This change in pharmacologic response has the characteristics of functional rather than pharmacokinetic tolerance in that there was no change in the drug concentration profile with time and no effect of the manipulations as such (i.e., repeated pain threshold determinations and blood withdrawals) on diflunisal-induced analgesia. These observations may have important implications for the evaluation and use of non-narcotic analgesics in the management of clinical pain.     

Effect of beta-casomorphin on neonatal sleep in rats

The effects of bovine beta-casomorphin(1-7) (Tyr-Pro-Phe-Pro-Gly-Pro-Ile) on neonatal sleep in rats were studied. The pups received intraperitoneal injections of beta-casomorphin(1-7) (1 mg, 5 mg, 10 mg, 50 mg, or 100 mg/kg) or a corresponding volume of sodium chloride. In any of the doses used, beta-casomorphin(1-7) had no effect on waking. Only 100 mg/kg caused significant changes in sleep: the percentage of quiet state of the total recording time (TRT) increased and the percentage of active sleep decreased. Beta-casomorphin(1-7) did not cause significant respiratory depression. Naloxone pretreatment (1 mg/kg IP) reversed the effects of beta-casomorphin(1-7) on sleep, a finding which suggests that opiate mu-receptors are involved in mediating the sleep effects of beta-casomorphin.     

Effects of naloxone on plasma corticosterone in the opiate-naive rat

Naloxone HCl (NX) has long been considered to be a pure narcotic antagonist, having an effect only subsequent to pretreatment with a narcotic. Characteristically, low doses of NX have been used to antagonize the effects of analgesic doses of narcotics and to precipitate withdrawal in chronically treated animals. In this study, the effects of high doses of NX (2.0–20.0 mg/kg) on changes in plasma corticosterone were examined in the opiate-naive animal. Using male rats with chronic intravenous catheters and one-way vision boxes, injections were made and serial blood samples were obtained in the conscious, unrestrained animal. The acute administration of NX to the opiate-naive animal produced a dose-related increase in plasma corticosterone with respect to both amplitude and duration. NX (10.0 mg/kg i.v.) produced a significant elevation in hormone level at 15 and 30 minutes. With NX (20.0 mg/kg i.v.) the duration of the response was extended to 60 minutes. To examine whether short-term tolerance to this effect could be produced, animals were given a single pretreatment with either NX (10.0 mg/kg) or saline i.v. Two hours later NX produced a similar elevation in hormone level in both groups. The effect of chronic injection of NX was also studied. Animals pretreated with either NX (10.0 mg/kg) or saline s.c. once daily for 7 days did not show a significant difference following the subsequent administration of NX. In both cases, a significant elevation of plasma corticosterone resulted. The results suggest that NX may have a direct effect on opiate receptors resulting in an elevation of plasma hormone levels or NX may be disrupting an endogenous opiate-receptor interaction producing a stress response.     

The effect of adrenaline pretreatment on the in vitro generation of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine (reverse T3) in rat liver preparation

The effects of adrenaline (A) on liver T3 and rT3 neogenesis from T4 were studied in Wistar rats. The animals were implanted subcutaneously either with A or placebo (P) especially coated tablets which linearly released the hormone. The serum A values 6 hrs after implantation of 7.5, 15.0 and 45.0 mg tablets were 6.5 +/- 1.31, 6.8 +/- 1.8 and 16.4 +/- 1.9 ng/ml, respectively vs 4.4 +/- 2.5 ng/ml seen in P pretreated group. The output rates of A were 0.11 (7.5 mg), 0.18 (15 mg) and 0.52 microgram/ml (45 mg). The pretreatment with A led to hyperglycemia and the "low T3 syndrome". Neogenesis of T3 from T4 in medium containing liver microsomes of P pretreated rats was 5.49 +/- 0.25 pmol of T3/mg protein/min and decreased in A pretreated rats to 3.82 +/- 0.17, 3.12 +/- 0.27 and 3.06 +/- 0.11 pmol of T3/mg of protein/min. Neogenesis of rT3 from T4 in microsomes from P group was 1.52 +/- 0.09 pmol rT3/mg protein/min and increased after A to 2.71 +/- 0.11, 2.60 +/- 0.21 and 2.21 +/- 0.34 pmol of rT3/mg protein/min thus showing no dose dependency. Enrichment of microsomes medium with cytosol either from P or A pretreated rats had no effect on T3 generation thus excluding effect of A on cytosolic cofactor. Although cytosol further increased rT3 neogenesis this was seen regardless of whether cytosol was obtained from A or P implanted rats. It is concluded that A decreases the activity of T4-5'-deiodinase in liver, and possibly increases the activity of T4-5-deiodinase.     

Modification of Morphine-induced Hyperlocomotion and Antinociception in Mice by Clorgyline,a Monoamine Oxidase-A Inhibitor

We evaluated the effects of pretreatment with clorgyline, an irreversible monoamine oxidase (MAO)-A inhibitor, on morphine-induced hyperlocomotion and antinociception. A single administration of morphine (30 mg/kg, i.p.) to male ICR mice induced a hyperlocomotion. ANOVA analysis revealed the statistical significance of the morphine effect on horizontal locomotion and of the clorgyline pretreatment × morphine interaction effect, but not of the effect of clorgyline pretreatment. The initial (5 min after challenge) phase of morphine actions vs. saline challenge appeared as if morphine had a strong inhibitory effect on locomotor activity in combination with different doses of clorgyline. The mice administered with morphine in combination of clorgyline (1 and 10 mg/kg) did not show any stereotypic behaviors. Clorgyline at a dose of 0.1 mg/kg but not other doses tested significantly potentiated morphine-induced antinociception evaluated by tail flick but not hot plate test. During the measurements of locomotor activity and antinociception, clorgyline at doses of 1 and 10 mg/kg significantly inhibited monoamine metabolism through MAO. These results suggest that clorgyline showed an inhibitory effect on morphine-induced hyperlocomotion, but not antinociception, through MAO inhibition. There is not a possibility that clorgyline pretreatment enhanced morphine action on motor activity, resulting in the abnormal behavior from hyperlocomotion to stereotypic movements.     

Cadmium administration and hepatic drug metabolizing enzyme system: effect of pretreatment with phenobarbital and 3-methyl cholanthrene

A single dose of cadmium sulphate (2 mg/kg, ip) produced variable effects on the components of hepatic microsomal enzyme system in untreated, phenobarbital and 3-methyl cholanthrene pretreated rats. Measurements of the activities of these components showed that phenobarbital pretreatment prevented the decrease in the specific activity of benzphetamine demethylase, as well as decrease in the contents of cytochrome P-450 and phosphatidyl choline seen in rats given cadmium alone. In contrast, prior administration of 3-methyl cholanthrene did not protect against the inhibitory effect of the metal on cytochrome P-450 and phospholipid components. However, the dose of cadmium used in this study did not appear to have any significant effect on the activities of cytochrome P-450 reductase and aniline hydroxylase.     

Prostacyclin-like activity in rat vascular tissues. Fast, long-lasting inhibition by treatment with lysine acetylsalicylate.

Both arterial and venous tissues obtained from normal rats released prostacyclin (PGI2)-like activity, as marked by its potent inhibitory effect on platelet aggregation. Intraperitoneal or intravenous administration of a single dose of a soluble lysine salt of acetylsalicyclic acid (L-ASA, 1-400 mg/kg) resulted in abolition or substantial reduction of prostacyclin-like activity released from rat vasculature. The inhibitory effect of L-ASA was evident one minute after its i.v. administration to the animals, persisted for at least 24 hours and was still detectable (in venous tissues only) 168 hours later. Venous tissues were inhibited by doses of L-ASA as low as 1 mg/kg, whereas arterial tissues were not inhibited by doses of LA-ASA lower than 10 mg/kg. This difference may possibly be related to the lower prostacyclin-like activity shown by rat venous tissues compared to arterial ones. It is suggested that L-ASA or part of its molecule may bind to and inhibit cyclo-oxygenase in the blood vessel wall in a manner similar to the acetylation of platelt cyclo-oxygenase.