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1.
Analgesic effects of dynorphin-A and morphine in mice 总被引:3,自引:0,他引:3
To investigate whether or not dynorphin-A is analgesic, the effect of this peptide was tested in comparison with that of morphine in mice. Dynorphin-A produced a potent analgesic effect in the acetic acid writhing and tail pinch tests, but a weak effect in the tail flick test when given by intracerebroventricular injection. In contrast, morphine caused a potent analgesia in all the tests. Dynorphin-A was more effective when given by intrathecal injection than by intracerebroventricular injection, whereas morphine was equipotent by both injection routes. The results suggest that dynorphin-A is analgesic and that its analgesia may be differentiated from that of morphine. 相似文献
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Tj.B. Van Wimersma Greidanus D.K. Donker R. Walhof J.C.A. Van Grafhorst N. De Vries S.J. Van Schaik C. Maigret B.M. Spruijt D.L. Colbern 《Peptides》1985,6(6):1179-1183
The influence of naloxone, haloperidol and neurotensin was investigated on bombesin-induced excessive grooming in rats. All three drugs reduced the amount of bombesin-induced grooming. Haloperidol induced a general reduction in excessive grooming as induced by bombesin, without changing the composition of grooming behavior, whereas naloxone and neurotensin suppressed bombesin-induced grooming and caused a shift in the distribution of grooming elements. The main suppressive effect of these latter drugs appeared to be on the element scratching. From these data it is suggested that bombesin-induced scratching is mainly displayed by activation of opiate receptor systems, whereas the other elements of bombesin-induced excessive grooming are mainly regulated by dopaminergic systems. 相似文献
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Dynorphin is a recently identified, pharmacologically potent endogenous opioid peptide. Heretofore it has not been characterized for its behavioral effects. The effects of centrally infused dynorphin upon a variety of behaviors were therefore examined in mice and rats. The present findings point to a specific profile of behavioral activity. The peptide was active in facilitating feeding and grooming, but was inactive in modifying pain sensitivity and rearing behavior. Naloxone was generally ineffective in reversing behavioral effects. Dynorphin thus appears to have some opiate-like effects upon exogenous administration but may be rapidly broken down into a behaviorally potent non-opiate peptide fragment. 相似文献
4.
Dynorphin is a recently identified, pharmacologically potent endogenous opioid peptide. Heretofore it has not been characterized for its behavioral effects. The effects of centrally infused dynorphin upon a variety of behaviors were therefore examined in mice and rats. The present findings point to a specific profile of behavioral activity. The peptide was active in facilitating feeding and grooming, but was inactive in modifying pain sensitivity and rearing behavior. Naloxone was generally ineffective in reversing behavioral effects. Dynorphin thus appears to have some opiate-like effects upon exogenous administration but may be rapidly broken down into a behaviorally potent non-opiate peptide fragment. 相似文献
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Heroin, α--acetylmethadol (LAAM), morphine, and methadone each maintained self-administration in rhesus monkeys. The order of relative potency was heroin ≥ LAAM > morphine ≥ methadone. Total daily drug intake increased as dose per injection increased; maximum daily intake was inversely related to relative potency. At high doses, self-injection of methadone and LAAM caused stupor and/or respiratory failure in some monkeys. These toxic effects were partly or completely reversible by naloxone. 相似文献
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Effects of various dipeptides on naloxone-precipitated morphine withdrawal were studied in the mouse. Mice were rendered dependent on morphine by implantation of morphine pellets and the withdrawal syndrome was measured by the latency of the onset of stereotyped jumpings. In accordance with previous data, subcutaneous injection of Z-prolyl-D-leucine significantly delayed the onset of morphine withdrawal. The all-L enantiomer of the dipeptide (Z-L-prolyl-L-leucine) did not affect morphine withdrawal in the dose studied. Replacement of L-proline by L-glutamate or L-pyroglutamate (Z-L-glutamyl-L-leucine and L-pyroglutamyl-L-leucine) resulted in dipeptides which were more potent towards morphine withdrawal than Z-prolyl-D-leucine. Z-L-glycyl-L-proline attenuated the morphine withdrawal syndrome more effectively than Z-L-prolyl-D-leucine, but Z-L-leucyl-L-glycine was ineffective in this respect. The data reveal that certain dipeptides—which in their nonprotected forms are normal sequences of endogenous peptides—affect morphine withdrawal more potently than Z-prolyl-D-leucine, a synthetic dipeptide known to attenuate morphine dependence. 相似文献
7.
Footshock induced analgesia in mice: its reversal by naloxone and cross tolerance with morphine 总被引:4,自引:0,他引:4
Using the abdominal constriction response as the criterion for analgesia, mice tested immediately after a period of footshock showed a significant analgesic response compared with non-footshocked controls. Footshock induced analgesia could not be elicited in mice that had been made tolerant to morphine or in mice that had been pretreated with the narcotic antagonist naloxone. It is concluded that footshock induced analgesia in the mouse is due to the release of endogenous opioid peptides. 相似文献
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Dosing-time-dependent changes in the effect and toxicity of morphine were examined in mice housed under alternating 12 h light (07:00 to 19:00 h) and dark (19:00 to 07:00 h) cycles. Morphine (0.5 mg/kg) was injected intraperitoneally (i.p.) in animals to assess its beneficial effect (i.e., protection against the kaolin-induced, bradykinin-mediated, writhing reaction) and its toxicity (i.e., alteration of the hepatic enzymes of aspartate aminotransferase [AST] alanine aminotransferase [ALT], and glutathione [GSH] in separate experiments). The magnitude of the analgesic effect of morphine depended on dosing time, with minimum effect at 02:00 h and maximum effect at 14:00 h. The serum hepatic enzyme levels of AST and ALT increased after dosing morphine (100 mg/kg) at 02:00 and 14:00 h. Time courses of these enzymes did not differ between the two trials. However, hepatic GSH, which is involved in the detoxification of chemical compounds, significantly decreased after i.p. morphine injection at 02:00 but not at 14:00 h. Overall, the results suggest that the analgesic effect of morphine is greater after dosing during the resting than during the activity phase of mice that have been induced with bradykinin-mediated pain. Drug-induced hepatic damage as inferred by GSH alteration, however, may be greater after dosing during the active phase. 相似文献
11.
Subplantar injection of Brewer's yeast induces a hyperalgesia that is associated with an increase in the level of striatal Met-enkephalin (ME); there was no change in the hypothalamus of periaqueductal gray. To test the relationship between striatal ME and analgesia, naloxone (10, 3, 0.5 mg/kg, SC) or thiorphan (100 μg, ICV) were administered. Neither drug caused a potentiation or a reduction in the hypersensitivity. These data suggest that an increase in striatal ME does not result in altered pain sensitivity in this model. 相似文献
12.
S U Hasan C Pinsky D B Cates B J Nowaczyk D A Gibson H Rigatto 《Journal of developmental physiology》1990,14(3):171-179
In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal. 相似文献
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Previous studies suggested that ceruletide might be endowed with analgesic and sedative properties. To investigate the effects of ceruletide on experimentally induced pain and on central nervous functions, two studies, each involving 24 healthy subjects, were carried out in random double-blind fashion. Every subject participated in three experiments one week apart. In study 1, 120 and 60 ng/kg/hr ceruletide IV increased threshold and tolerance to electrically and threshold to thermally induced cutaneous pain significantly more than saline (p<0.001), the higher dose being slightly more active. Only mild sedative effects occurred. Study 2 compared the effects of 60 and 6 ng/kg/hr ceruletide IV to those of 0.4 mg/kg/hr pentazocine IV and investigated whether these effects were naloxone reversible. Both ceruletide doses, 60 ng/kg/hr slightly more than 6 ng/kg/hr, elevated threshold and tolerance to electrically induced and threshold to thermally induced pain markedly, pentazocine acted stronger and longer than ceruletide (p<0.001). Naloxone reversed the effects of pentazocine but not of ceruletide. Conclusion: ceruletide (1) exerts potent naloxone resistant analgesic effects, which, however, are inferior to those of pentazocine, and (2) produces only mild sedation. 相似文献
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Quantitative autoradiography of [14C]deoxyglucose, [14C]iodoantipyrine, and [14C]leucine was used to estimate regional cerebral glucose metabolism, cerebral blood flow, and cerebral protein synthesis, respectively, in rats during morphine dependence and withdrawal. Glucose metabolism was elevated in 19 of 26 selected brain regions; the elevations in glucose metabolism were similar when data were expressed as either optical density ratios or as calculated rate values of mol/100 gm/min. Restraining the rats produced heterogeneous effects on glucose metabolism during morphine withdrawal (MW). Neither estimated cerebral blood flow nor cerebral protein synthesis were affected by morphine and/or naloxone treatments in either naive or morphine-dependent rats. The data demonstrate that changes in regional cerebral glucose utilization occur independently of blood flow changes and exclude the possibility that regional changes in glucose utilization occur as a consequence of large regional changes in protein synthesis rates in brain. These data confirm the utility of 2-deoxyglucose measures of MW as objective biochemical indices of opiate agonist and antagonist effects in vivo. 相似文献
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Interactions of prostaglandin E1 (PGE1) with morphine have been reported in several test systems and an hypothesis has been advanced for a role of prostaglandins in morphine analgesia and physical dependence. In rats self-administering morphine intravenously, a simultaneous and continuous infusion of naloxone hydrochloride at 56 to 560 μg/kg/day caused the expected increase in injection rate for morphine. Infusion of PGE1 by itself at 56 or 180 μg/kg/day had no effect on the rate of morphine intake. Likewise the addition of PGE1 at 180 μg/kg/day did not potentiate the increase caused by naloxone (56 or 180 μg/kg/day) when it was added to the naloxone infusion. These results do not support a role for prostaglandins in the behavioral aspects of morphine addiction. However, larger doses of PGE1 (1 and 1.8 mg/kg/day), which were without overt effects in normal rats, caused severe and incapacitating prostration in morphinized rats. 相似文献
16.
Larry D. Byrd 《Life sciences》1983,32(4):391-398
Heart rate (HR) and mean arterial blood pressure (BP) were recorded from conscious, chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous injections of two opiate antagonists and an agonist. Naloxone (0.3–10.0 mg/kg) or naltrexone (0.3–10.0 mg/kg) had little effect on HR or BP during a 30-minute post-injection period. Morphine (3.0–5.6 mg/kg) produced biphasic effects comprising an initial decrease followed by an increase in HR, and an increase followed by a decrease in BP. Lower morphine doses had lesser effects during a 100-minute post-injection period. Pre-treatment with 0.03 mg/kg naloxone attenuated the depressive effect of morphine on HR and BP, but increases in HR and BP due to morphine were enhanced. Pretreatment with 0.3 mg/kg naloxone prevented morphine-induced decreases in HR and BP, yet increases in HR and BP persisted. In previous behavioral studies, morphine in combination with naloxone similarly increased rates of responding in the squirrel monkey. Together, these data suggest an effect of naloxone that goes beyond mere pharmacological antagonism of the effects of morphine. 相似文献
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This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics. 相似文献
18.
本工作用制备 Thomas 胰瘘和胃痿的5条狗进行慢性实验。实验时用0.1N 盐酸灌入十二指肠以刺激胰液分泌,并分別注射吗啡或/和纳洛酮,观察它们对胰液分泌和对胰液中碳酸氢盐和蛋白质浓度的影响。另外我们还观察了吗啡和纳洛酮对6条狗离体胰主导管紧张性的影响。结果表明:(1)吗啡抑制了胰液分泌量,对胰液中碳酸氢盐和蛋白质浓度无影响,由于分泌量减少故两者的排出量显著减少(P<0.05),(2)纳洛酮本身对胰液分泌量和碳酸氢盐及蛋白质浓度均无影响;(3)纳洛酮可以加强吗啡抑制胰液分泌的作用(P<0.01);(4)吗啡能增加狗的离体胰主导管肌条的紧张性,纳洛酮不能阻断或翻转吗啡的这一效应,相反能加强其效应。本工作表明,吗啡抑制酸化十二指肠所引起的胰碳酸氢盐和蛋白质排出量,其机制可能是吗啡刺激胰导管收缩,而纳洛酮则加强吗啡的这种抑制效应。 相似文献
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Evidence for sedative effects of low doses of morphine in mice involving receptors insensitive to naloxone 总被引:1,自引:0,他引:1
Low doses of morphine (0.30–2.5 mg/kg) decrease in a dose-dependent manner spontaneous climbing behaviour in mice. This effect is not modified by administration of naloxone at doses up to 1.25 mg/kg. These morphine doses do not modify the locomotor activity but, when they are associated with naloxone (0.5 mg/kg), an obvious inhibition occurs. In rats, a hyperactivity follows the akinesia produced by a morphine administration (10 mg/kg). This hyperactivity is changed into a significant hypokinesia when the animals are treated with naloxone (0.05 mg/kg). These results might reveal a dual effect of low doses of morphine, the excitatory effect of morphine being antagonized by naloxone whereas no action on the sedative effect is observed. 相似文献