1,720,980 research outputs found
Quantitative evaluation of opioid withdrawal signs in rats repeatedly treated with morphine and injected with naloxone, in the absence or presence of the antiabstinence agent clonidine
No full textAn opioid withdrawal syndrome was induced in rats by repeated morphine administration and final naloxone injection. The withdrawal causes alteration of several physiological signs. The aim of the study was to describe a quantitative opioid abstinence syndrome to validate the methodology by utilizing clonidine, a well-known antiwithdrawal agent, and propose the procedure for the screening of antiabstinence drugs. In particular, rats were treated with saline, morphine, naloxone, morphine and naloxone and four doses of clonidine (0, 0.04, 0.1, and 0.25 mg/kg orally). In rats repeatedly exposed to morphine and then injected with naloxone, signs like excretion of feces and urine, salivation, behavioral jumping and wet dog shakes, rectal temperature, and pain threshold have been observed. Consequently, the objective symptoms observed in morphine plus naloxone-treated animals have been taken as markers of opioid withdrawal. These factors have been quantitatively measured and grouped to form a standardized procedure of opioid abstinence syndrome. In addition, it is possible to observe that the antiabstinence drug clonidine exerted effects on modified physiological signs appearing in morphine-dependent rats treated with naloxone, like fecal excretion, levels of rectal temperature, latency times, salivation as well as jumping behavior. The effects exerted by clonidine in this procedure and in other methods are compared and appear to be similar. In addition, comparative observations referring to both the previous methods and the present procedure related to the type of signs studied, the modality of evaluation, and suppressive activity exerted by the antiwithdrawal agent, clonidine, are performed: the greater accuracy of the proposed method becomes apparent. Thus, this experimental model, validated by the antiabstinence agent clonidine, is proposed as a useful screen for drugs affecting opioid withdrawal syndrome
Effects of administration of phentonium bromide on opioid withdrawal syndrome in rats
No full textThis study has tested whether phentonium bromide, a quaternary ammonium anti-muscarinic agent, could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days, after which half the rats received naloxone and half saline. Each animal also received one of four doses of phentonium bromide (0, 1, 3 and 9 mg kg(-1), i.p.). Administration of phentonium bromide in rats receiving naloxone after chronic morphine treatment reduced the intensity of withdrawal signs such as increased defecation or micturition, salivation and wet-dog shakes, and elevated the nociceptive threshold values. The effects of administration of phentonium bromide might result from its anti-muscarinic activity interfering peripherally with the mechanisms involved in the regulation of the withdrawal symptoms. The use of this drug is thus suggested as a possible means of controlling some of the signs observed during the acute phase of opioid withdrawal in heroin addicts
Effects of tizanidine administration on precipitated opioid withdrawal signs in rats
No full textAn opioid withdrawal syndrome was precipitated by naloxone administration in rats treated with morphine. The withdrawal caused alteration of several physiological signs. The aim of the study was to investigate whether the altered physiological profiles were modified by utilising tizanidine, an alpha 2 adrenergic receptor agonist which is capable of affecting faecal and urinary excretion, rectal temperature, pain threshold levels and salivation. To induce an opioid withdrawal syndrome, morphine was administered in three daily intraperitoneal injections for four days at doses of 9, 16 and 25 mg/kg (1st day), 25, 25 and 50 mg/kg (2nd day), 50, 50 and 50 mg/kg (3rd day) and 50, 50 and 100 mg/kg (4th day): naloxone was injected (30 mg/kg) i.p. 180 min after the last morphine injection. Tizanidine was administered orally at 0.17, 0.35 and 0.7 mg/kg, 60 min after the last morphine injection. Signs such as faecal and urine excretion, rectal temperature and latency times to thermal stimulus, salivation, jumping and wet dog shakes were affected in different ways by morphine, naloxone, tizanidine and by the combination of these agents. Notably, the administration of tizanidine in rats receiving morphine and naloxone decreased the intensity of certain withdrawal symptoms, including altered excretion of faeces and urine, salivation and wet dog shake behavior. Body temperature levels and nociceptive threshold values were also modified. The effects caused by tizanidine administration may be due to its alpha 2 receptor agonist activity interfering with a mechanism involved in the regulation of these previously mentioned withdrawal symptoms. Thus, the use of this drug may be indicated as a possible control of the acute phase of opioid withdrawal in heroin addicts
Effects exerted by otilonium bromide administration on precipitated opioid withdrawal syndrome in rats
No full textAn opioid withdrawal syndrome was induced in rats by repeated morphine administration and final naloxone injection. The withdrawal causes alteration of several physiological signs. The aim of the study was to prevent the altered physiological profiles by utilising otilonium bromide. Morphine was administered in three daily i.p. injections for 4 days at doses of 9, 16 and 25 mg/kg (1st day), 25, 25 and 50 mg/kg (2nd day), 50, 50 and 50 mg/kg (3rd day) and 50, 50 and 100 mg/kg (4th day). Naloxone was injected (30 mg/kg) i.p. 180 min after the last morphine injection. Otilonium bromide was administered orally at 0, 2, 4 and 8 mg/kg, 120 min before the naloxone administration. Signs like faecal and urine excretion, rectal temperature and pain threshold levels, salivation, jumping and wet dog shakes were affected in different ways. Notably the administration of otilonium bromide in rats receiving morphine together with naloxone decreased the intensity of certain withdrawal symptoms, such as excretion of faeces, wet dog shake behaviour, and elevated the nociceptive threshold values. The effects exhibited by otilonium bromide administration may be explained through its calcium antagonist activity interfering with a mechanism involved in the regulation of these previously mentioned withdrawal symptoms. The use of this drug is thus suggested as a possible control of some acute opioid withdrawal signs in heroin addicts
Activated partial thromboplastin time correlates with methoxyhydroxyphenylglycol in acute myocardial infarction patients : therapeutic implications for patients at cardiovascular risk
No full textBACKGROUND/AIM: Acute myocardial infarction (AMI) is associated with increased coagulation which in the presence of unstable atheroma or endothelial damage leads to occlusive coronary vessel thrombosis. AMI is usually characterized by increased levels of catecholamines. It is possible there may be a link between catecholamines and hypercoagulation, but this still remains to be determined. In the current study we sought to verify whether hypercoagulation is associated with hypersympathetic activity in AMI patients, and whether there is a correlation between increased Methoxyhydroxyphenylglycol (MOPEG) levels (a metabolite of catecholamines) and shorter APTT (a marker of hypercoagulation).
RESULTS: Shorter APTT values were detected in the plasma of AMI patients, which had also increased MOPEG levels. A linear correlation between APTT and MOPEG values was observed. High levels of the coagulation marker prothrombin (fragments 1+2) were also found.
CONCLUSION: Shortened APTT demonstrates hypercoagulation and high MOPEG levels indicate increased catecholamine metabolism. A direct correlation between APTT and MOPEG was found herein, demonstrating a link between catecholamines and the process of coagulation. Catecholamines may interact with the α2-adrenergic receptors located on platelets and convert factor XII to XIIa or through the kallikrein-kinin system, they may activate factor XII. The activation of factor XII initiates the intrinsic coagulation pathway, which is monitored by APTT. It is suggested to control patients with a shortened APTT and increased sympathetic activity with the aim of preventing secondary coagulation and cardiovascular accidents by administering anti-thrombotic and anti-adrenergic agents
Quantitative opioid withdrawal signs in rats : effects exerted by clothiapine administration
No full textAn opioid withdrawal syndrome, which causes alteration of several physiological signs, was induced in rats by repeated morphine administration and final naloxone injection. The aim of this study was prevention of the altered physiological profiles by utilising clothiapine, which is capable of affecting fecal and urinary excretion, rectal temperature, pain threshold levels and salivatory behaviour. Morphine was administered in three daily intraperitoneal (ip) injections for 4 days at doses of 9, 16 and 25 mg/kg (d 1), 25, 25 and 50 mg/kg (d 2), 50, 50 and 50 mg/kg (d 3) and 50, 50 and 100 mg/kg (d 4). Naloxone was injected (30 mg/kg) ip 180 min after the last morphine injection. Clothiapine was administered orally 0.7, 2 and 6 mg/kg 2 hours before the naloxone administration. Signs such as fecal and urine excretion, rectal temperature and latency times to thermal stimulus salivation, jumping and wet dog shakes were affected in different ways by morphine, naloxone, clothiapine and combination of them. Notably the administration of clothiapine in rats receiving morphine and naloxone decreased the intensity of certain withdrawal symptoms, such as altered excretion of feces, temperature values, salivation, jumping and wet dog shakes behaviour, and elevated the nociceptive threshold values. The effects exhibited by clothiapine administration may be explained through its antimuscarinic, antiadrenergic and antidopaminergic activities interfering with the mechanisms involved in the regulation of these previously mentioned withdrawal symptoms. The use of this drug is thus suggested as a possible control of the acute phase of opioid withdrawal in heroin addicts
Effects of alpha-lipoic acid administration on plasma glucose levels, total malondialdehyde values and withdrawal signs in rats treated with morphine or morphine plus naloxone
No full textMorphine (CAS 57-27-2) administration or its removal induces alterations in glucose levels and oxidative status or behaviour signs, which may be hypothetically closely related; if this is correct, controlling glucose changes may lead to modifications in peroxide levels and in behaviour profile. It therefore seems important to rind a drug able to control alterations of glucose metabolism, peroxide generation and behaviour symptoms in morphine or morphine withdrawal animals. This paper describes the effects of morphine or morphine plus naloxone (CAS 51481-60-8) on the plasma levels of glucose, malondialdehyde (MDA) (CAS 100683-54-3) and behavioural signs in rats treated or not with alpha-lipoic acid (CAS 1077-28-7), known to interfere with glucose and peroxide levels.The administration of morphine or its removal by naloxone alters plasma glucose levels, increases MDA values, and also affects signs such as pain threshold values, fecal excretion and jumping behaviour.The injection of alpha-lipoic acid decreases glycemia in rats treated with morphine or morphine plus naloxone. This result may be due to the capacity of alpha-lipoic acid to facilitate glucose transport and its utilization. The administration of alpha-lipoic acid to rats given morphine or morphine plus naloxone lowers total MDA levels because of its peroxide scavenging capacity. In animals injected with morphine plus naloxone, which show altered pain thresholds, high fecal excretion and jumping behaviour, treatment with alpha-lipoic acid increases latency times, decreases fecal excretion and reduces jumping. These effects can be attributed to the capacity of alpha-lipoic acid to interfere with mediators or peroxides involved in the modified behaviour. The glycemia levels, MDA values and behavioural signs seem to be interconnected in the reported experiments. The administration of alpha-lipoic acid is demonstrated to control the alterations in plasma glucose levels, peroxide values or behavioural profile in animals receiving morphine or morphine plus naloxone
Effects of carbamazepine treatment on pain threshold values and brain serotonin levels in rats
No full textThe administration of carbamazepine to rats caused a significant increase in pain threshold values. Furthermore, treatment with carbamazepine lowered the concentration of tryptophan bound to plasma proteins and elevated the brain serotonin values. The high brain serotonin levels, observed in carbamazepine-treated rats, are probably attributable to an increased availability of brain tryptophan, since this amino acid has been substantially removed from the plasma protein compartment by carbamazepine treatment, which exhibits a high binding capacity to plasma proteins. The analgesic effects caused by carbamazepine administration have been attributed to increased levels of brain serotonin which is involved in the control of pain transmission
High-dose vitamin E lowers urine porphyrin levels in patients affected by porphyria cutanea tarda
No full textPorphyria cutanea tarda (PCT) is a metabolic disorder of heme biosynthesis, characterized by reduced uroporphyrinogen decarboxylase (UROD) activity and increased urinary excretion of eight and seven carboxyl group porphyrins. Specific factors such as iron, alcohol and halogenated compounds further inhibit enzyme activity by generating reactive oxygen species. Antioxidant vitamin E has frequently been used to counteract oxidative stress in porphyria patients, but a number of studies have failed to detect any significant effect on porphyrin metabolism. Since the use of vitamin E in the treatment of porphyria is a debated question, it seemed of interest to administer high doses to five patients with PCT in order to evaluate the effects on urine porphyrin excretion. The patients had high urinary porphyrin excretion levels, but vitamin E significantly reduced the urinary excretion of eight carboxyl group porphyrins. This result is attributable to the increase in UROD activity caused by the vitamin, which is a known scavenger of the oxygen reactive species that interfere with the activity of the enzyme. In conclusion, this paper shows that vitamin E high doses significantly lowers the urine porphyrin excretion in studied patients affected by PCT. Copyright 2002 Elsevier Science Ltd. All rights reserve
Antisecretory activity of 6-aminoindazole in rats
No full textAdministration of 6-aminoindazole (6-AIN) and 5-aminoindazole (5-AIN) to rats depressed gastric acid secretion, both basal and carbachol-stimulated. 6-AIN proved to be more active than 5-AIN in decreasing the stimulated secretory process. The antisecretory activity of 6-AIN appears to be partially an antihistamine effect, since this compound antagonized the stimulatory action of betazole on isolated guinea pig auricle. The antisecretory activity of 6-AIN is probably associated with an antimuscarinic effect, since the molecule decreased carbachol-stimulated gastric acid secretion in rats and depressed neostigmine-stimulated motility of duodenum and colon in the anaesthetized cat. It also lessened the hypertonus of isolated guinea-pig trachea caused by pilocarpine. The antisecretory effects of 6-AIN also appear to be associated with myolytic activity, since it decreased the spontaneous motility of duodenum and colon in anaesthetized cats and the spontaneous myoactivity of isolated jejunum of the rabbit. It depressed the contractions of isolated guinea-pig ileum caused by histamine and decreased the spasmogenic effects of barium chloride on isolated guinea-pig gall bladder. These results suggest that 6-AIN probably depresses gastric acid secretion by interfering with both histamine and acetylcholine receptors and with other receptors involved in the secretory process
- …
