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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both naloxone and naltrexone are effective narcotic antagonists with minimal agonistic effects and a wide margin of safety. Naloxone is useful in the treatment of narcotic overdose and it is helpful in the quantification of physical dependence. Naltrexone is pharmacologically successful as an orally effective, long-acting antagonist but its clinical usefulness in the prevention of relapse is still being determined.
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PMID:Clinical pharmacology of narcotic antagonists. 36 32

1. A slow release emulsion of naloxone (naloxone SR) was administered subcutaneously to rats in an attempt to induce physical dependence of the morphine type. 2. Naltrexone (2.5 mg/kg), injected i.p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h. 3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin. 4. Naloxone SR caused an apparent dose-related increase in the brain levels of 5-hydroxyindoleacetic acid. 5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate. 6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine-like drugs but may be a property of drugs containing the basic opiate molecular structure.
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PMID:Dissociation of increased 5-hydroxyindoleacetic acid levels and physical dependence: the effects of naloxone. 56 13

A single i.p. injection of naltrexone (20 mg/kg) partially inhibited the development of physical dependence upon morphine in mice rendered dependent on morphine by implantation of a pellet containing 75 mg of morphine free base for three days. This was evidenced by an increase in the dose of naloxone (ED50) required to precipitate withdrawal jumping response. The increase in naloxone ED50 was much more pronounced when naltrexone was given prior to and during the course of pellet implantation. Inhibition was also observed when naltrexone was administered one day after the morphine pellet implantation, i.e., after some dependence had already developed. Naltrexone administration prior to and during the development of dependence also inhibited, but only partially, the loss of body weight and hypothermic response observed during abrupt withdrawal of morphine in morphine-dependent mice. The inhibitory effect of naltrexone on morphine dependence development was not associated with changes in brain morphine concentration.
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PMID:The effects of naltrexone on the development of physical dependence on morphine. 56 85

Rats were trained to lever-press on a multiple-trial, fixed-interval, 3-min schedule of food-reinforcement; each trial consisted of a 10-min time-out and a 9.5-min response period. Naltrexone, injected s.c. prior to each trial, reduced response rates in a dose-related fashion, with an ED50 of 21 mg/kg. Four-hour pretreatment with i.c.v. morphine (3.0-30 micrograms) produced leftward shifts of the naltrexone dose-effect curve of up to 3 orders of magnitude. The selective mu agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO; 0.1-0.3 microgram i.c.v.), sensitized animals to the rate-decreasing effects of naltrexone by more than 2 orders of magnitude. Pretreatment with the selective kappa agonist, dynorphin A-(1-17) (30 micrograms i.c.v.) or the selective delta agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE; 30-100 micrograms i.c.v.) induced moderate sensitization with leftward shifts of 1.0-1.5 log units. Thus, the naltrexone-sensitizing effect of acute opioid pretreatment is centrally mediated, consistent with the hypothesis that the phenomenon is related to the initiation of opioid physical dependence. Further, the effect appears to be mediated predominantly by mu-opioid receptors, because mu agonists consistently produced the largest sensitization to naltrexone.
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PMID:Naltrexone-sensitizing effects of centrally administered morphine and opioid peptides. 167 8

Six female chronic spinal dogs were administered N-allylnormetazocine (NANM) chronically by the intravenous route starting at 0.3 mg/kg/day. The dose was escalated to a stabilization dose of 10 mg/kg/day. The dogs became tolerant to NANM's ability to produce canine delirium and its anorexigenic and respiratory stimulant effects. Naltrexone increased the amplitude of the flexor reflex and pulse rate in the body temperature, pupillary constriction, bradycardia and tachypnea. Appetite was decreased and weight was lost. These data indicate that chronic administration of NANM produces tolerance and a unique type of physical dependence. Some changes produced by chronically administered NANM were naltrexone antagonizable, others were not suggesting that NANM may have several mechanisms of action.
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PMID:Tolerance to and physical dependence on N-allylnormetazocine (NANM) in chronic spinal dogs. 689 Feb 39

1. The effect of naltrexone pellets containing either 10 or 30 mg of naltrexone base on the development of tolerance and physical dependence on morphine was assessed in male Sprague-Dawley rats. Tolerance-dependence on morphine was induced by s.c. implantation of six morphine pellets, each containing 75 mg morphine base for 7 days. 2. Naltrexone pellet implantation blocked the development of tolerance to the analgesic and hyperthermic effects of morphine. Similarly, naltrexone pellet implantation reversed morphine withdrawal-induced body weight loss. The effect of pellets containing 10 and 30 mg naltrexone did not differ. 3. The effect of naltrexone (10 mg) pellet implantation on various signs of naltrexone-precipitated withdrawal such as body weight loss, hypothermia and increases in urinary and fecal output was investigated. Naltrexone pellet implantation did not alter the naltrexone-precipitated withdrawal-induced body weight loss. Concurrent naltrexone pellet implantation blocked the naltrexone-precipitated withdrawal-induced hypothermia, increased fecal and urinary output in morphine-dependent rats. 4. These results indicate that a single pellet of 10 mg of naltrexone can effectively block morphine tolerance and physical dependence in the rat. Such a procedure may be useful in studying biochemical, endocrinological and immunological mechanisms involved in opioid addiction processes.
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PMID:Effects of naltrexone pellet implantation on morphine tolerance and physical dependence in the rat. 802

From March 1989 to February 1991, at "Telefono in Aiuto" (USL RM/10), Naltrexone has been used in 271 heroin addict patients. Naltrexone, a pure opiate antagonist, nullifies subjective heroin effects, preventing the setting up of tolerance and physical dependence. By administration for one year to drug-free addicts, it proved to be useful in relapse prevention. Naltrexone seems to be safe and without side-effects. Its effectiveness grows if its use is matched with psychological help.
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PMID:[Naltrexone therapy. Experience with "Telephone Assistance" in Rome]. 849 75

Naltrexone, a long-acting, orally effective, opioid antagonist which blocks opioid effects as well as the development of physical dependence, would appear to be a drug ideally suited to addiction treatment. An optimal dosage regimen is critical for the treatment patient compliance in ambulatory opiate detoxification programs. The ideal dosage regimen would be an oral controlled-release system of naltrexone that allowed once-a-day administration providing stable plasma levels. A naltrexone-Eudragit L complex was produced in aqueous medium from naltrexone hydrochloride solution and Eudragit L30D (30% w/v) previously diluted (6% w/v) and partially neutralized. The antagonistic activity of naltrexone-Eudragit L on morphine-induced thermal antinociception, in comparison with conventional naltrexone, was evaluated, using the mouse hot-plate model. Mice were administered 10 mg kg(-1) morphine subcutaneously, 10 min before test, and the antagonist products, either naltrexone-Eudragit L or naltrexone hydrochloride, were administered orally at 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16h before the test. The results showed that the antagonism induced by naltrexone-Eudragit L was effective until 12 h after drug administration, while that induced by naltrexone hydrochloride disappeared 10 h after its administration. A 23.47% increase of the area under curve was obtained when naltrexone-Eudragit L was administered, compared with that induced by conventional naltrexone. The time taken to decrease the inhibition of analgesic activity to 50% was delayed by 51.80%. This complexation technique can be considered as a useful tool in the design of oral controlled-release systems capable of inducing a long-lasting effect in-vivo.
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PMID:Preclinical study of an oral controlled release naltrexone complex in mice. 1087 42

In drug-free subjects, a single dose of morphine followed by an opioid antagonist a few hours later results in signs of a withdrawal syndrome, suggesting a state of physical dependence. Increased urination/defecation, altered startle, and ultrasonic vocalizations (USV) are some signs of the withdrawal syndrome in rats chronically dependent on morphine. We investigated whether naltrexone stimulates urination/defecation and alters startle and USV in male rats that were pretreated with only a single dose of morphine and compared these indices to the ones of chronic dependence. Separate groups of rats were pretreated with either a single dose (10 mg/kg) or with a continuous s.c. infusion of morphine via an osmotic pump. Naltrexone (0.01-1.0 mg/kg) was administered 2 to 6 h after the single dose of morphine and on days 7 to 11 of the infusion. Immediately after the naltrexone injection subjects were placed in sound-attenuating boxes to record startle and USV and to collect urine/feces. Subjects chronically exposed to morphine also were tested during spontaneous withdrawal 3 to 24 h after pump removal. Naltrexone increased urination/defecation in subjects pretreated with morphine either chronically or acutely; it increased startle and USV in acutely dependent rats but decreased them in chronically dependent rats. In the latter group, changes in the four variables during spontaneous withdrawal were qualitatively similar to those during precipitated withdrawal but smaller in magnitude. Differences in withdrawal signs between acute and chronic dependence suggest that the neural substrates that mediate those particular components of the withdrawal syndrome are affected differently in the two states of dependence.
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PMID:Changes in urination/defecation, auditory startle response, and startle-induced ultrasonic vocalizations in rats undergoing morphine withdrawal: similarities and differences between acute and chronic dependence. 1253 12