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

Biochemical and physiological theories of opiate addiction are reviewed in an historical context. The biochemical evidence implicating acetylcholine and norepinephrine in the phenomena of tolerance and physical dependence is described, and the six major biochemical and physiological theories are reviewed, emphasizing their close ties (differing sometimes only linguistically) with late nineteenth century theories of tolerance and physical dependence. The operational-reductionistic approaches taken by these theorists, especially when defining psychic dependence, is criticized from a phenomenological point of view while also emphasizing that characteristics of the social structure and moral viewpoints must also be taken into account when studying these phenomena.
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PMID:Biochemical and physiological approaches to opiate dependence. 1 51

1. Structure-activity relationship studies with new semi-synthetic isomorphine derivatives revealed that substitution of an azido group in position 6 (azidomorphines) greatly increases the analgesic potency whereas tolerance and dependence liability tend to decrease. 2. Azidomorphine (6-deoxy-6-azidodihydroisomorphine) and 14-hydroxyazidomorphine (6-deoxy-6-azidodihydro-14-hydroxyisomorphine) being in animal tests 40-300 times more potent than morphine, are the most effective analgesics among the semi-synthetic morphine alkaloids. 3. As demonstrated on mice, rats and rhesus monkeys, a remarkable dissociation between the analgesic potency and physical dependence capacity was the result of the introduction of the 6-azido group into dihydroisomorphine. 4. A dichotomy between analgesic effect and tolerance and addiction liability was demonstrated with azidomorphine also in man and the new substance proved to exert significantly less untoward effects than either morphine or pentazocine. 5. Rymazolium (Probon) a new non-narcotic analgesic which strongly potentiates the analgesic and antagonizes the respiratory depressant effect of morphine alkaloids in animals proved to hinder the development of tolerance to morphine in animals and man. 6. The azidomorphine-rymazolium association was found to be less respiratory depressant than azidomorphine administered alone. In patients with chronic intractable pain, an association of azidomorphine (0.5 mg) and rymazolium (150 mg) achieved total pain relief without noticeable euphoria and none of the twelve patients showed, according to the Himmelsbach scoring system, acute abstinence syndromes after nalorphine administration.
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PMID:Azidomorphines: a new family of potent analgesics with low dependence capacity. 4 67

Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 29 1/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, as a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.
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PMID:Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. 21 96

A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.
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PMID:An improved implantation pellet for rapid induction of morphine dependence in mice. 23 71

Experimental evaluation of Wikler's interoceptive conditioning hypothesis of relapse to opioid use in ex-addicts requires a preliminary study of the degree of physical dependence produced by two methods of drug administration. Wistar rats were made physically dependent on morphine by single daily intravenous injections or by a continuous i.v. infusion. Rats received the same total daily dose regardless of administration schedule. The initial daily morphine dose was 20 mg/kg, and was increased every fourth day by 20 mg/kg, until a dose of 200 mg/kg per day was reached. The rats were maintained at the highest dose level for 18 days, at which time morphine was discontinued. Body weight and water intake were the primary variables measured during addiction, maintenance, and abstinence phases of the study. Equivalent and parallel changes in mean weight and water intake in injection and infusion rats indicate equivalent degrees of physical dependence were developed. This finding allows separation of the contribution of conditioning factors and of protracted abstinence in facilitating opioid self-administration in formerly-dependent organisms.
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PMID:Interoceptive conditioning through repeated suppression of morphine-abstinence. I. Basis for conditioning: once-daily vs. continuous intravenous morphine infusion. 26 13

D-Histidine, administered in the 'wthdrawal' phase of morphine addiction, failed to modify the expression of tolerance and physical dependence in mice. L-Histidine, on the contrary, can enhance tolerance and inhibit physical dependence. Whole brain histamine is markedly increased by L-histidine administration, but only minimally by D-histidine. This confirms that the actions of L-histidine on morphine addiction are stereospecific, and so can be more confidently correlated with the increase in brain histamine levels produced by the natural amino acid precursor.
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PMID:The effects of D-histiding on the expression of morphine tolerance and physical dependence in mice. 56 20

1 General methods (chronic, subacute and acute) for assessing physical dependence potential, abstinence precipitating capacity and abstinence preventing activity are briefly presented. 2 Direct dependence experiments indicate that, in general, mixed agonist-antagonist analgesics have relatively lower physical dependence potentials than pure agonist analgesics. That of buprenorphine seems to be particularly low in various animal species. 3 When substitution techniques are used, the dependence potential of buprenorphine seems to be somewhat more developed than with direct dependence techniques. 4 Among various agonists (morphine, methadone and etorphine), antagonists (naloxone, naltrexone and diprenorphine) and mixed agonist-antagonists (pentazocine, butorphanol and buprenorphine), buprenorphine is the most potent and the longest acting drug in preventing precipitated abstinence in mice, rats and dogs. 5 The low physical dependence potential of buprenorphine may result in part from the very slow dissociation of the complex it forms with opiate receptors. This potential might be underestimated when precipitated abstinence methods are used, as naloxone would displace buprenorphine from its receptors only to a very limited extent. New means of evaluating dependence by more direct means need to be developed. 6 Overall, the properties of mixed agonists in general justify their use as analgesics with lower physical dependence potential than the pure opiates and further, those of buprenorphine seem to indicate its possible utility for the treatment of opiate addiction.
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PMID:Mixed agonist-antagonist opiates and physical dependence. 57 94

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 mug/kg/day caused the expected increase in injection rate for morphine. Infusion of PGE1 by itself at 56 or 180 mug/kg/day had no effect on the rate of morphine intake. Likewise the addition of PGE1 at 180 mug/kg/day did not potentiate the increase caused by naloxone (56 or 180 mug/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.
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PMID:Changes in morphine self-administration in rats induced by prostaglandin E1 and naloxone. 98 71

The effects of 1-(2-methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-piperazine-dihydrochloride (zipeprol, 3024 CERM, Respilene), a new nonopiate antitussive agent, have been studied on the cardiovascular system, intestinal function and the central nervous system. Most of these studies were performed comparatively with reference antitussives, particularly codeine, whose activites in these fields are the basis of its undesirable side effects. In the dog, zipeprol showed no hypotensive or cardiac-depressant activity. It did not alter pulmonary arterial pressure. An important antiarrhythmic action was apparent in studies on rhythm disturbances induced by ouabain and coronary ligation. Intestinal function, measured by the recording of peristaltic movements in the dog and the speed of intestinal transit in the rat, was not modified by the product. Zipeprol showed no characteristic action on the central nervous system. Analgesic activity was seen only at doses just below toxic levels. Finally in the rat and the mouse, no evidence of physical dependence was seen after prolonged treatment. This together with the absence of chemical similarity to the morphinics, leads to exclude the possibility of zipeprol treatment leading to addiction. The results of these studies allow zipeprol to be clearly distinguished from the opiate antitussives.
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PMID:General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). II. Actions on the cardiovascular system, intestinal transit and central nervous system. 98 57

Physical dependence on methadone was induced in rats by an initial "forced drinking" procedure and subsequently by i.p. administration of the drug. In a subsequent Experimental Phase of the study the physical dependence of one group was sustained by a "methadone maintenance" treatment, while two other groups were withdrawn from the drug, one gradually and one abruptly. When relapse trials were carried out during a Readdiction Phase it was found that the maintained group voluntarily consumed significantly greater amounts of methadone than did the two withdrawal groups. These groups did not differ between themselves but did in turn ingest significantly more methadone than a control group with no prior exposure to the drug. The characteristic loss of body weight reliably found during withdrawal from morphine was not demonstrated. This may have been due to the unexpected weight loss which occurred during the last stage of the initial Addiction Phase. The dependent variables of amount of methadone solution and the percentage of fluid consumed as methadone solution correlated highly. However the amount of methadone solution ingested was a better indicator of addiction liability as it was not influenced by fluctuations in the amount of water consumed by the animals.
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PMID:Methadone dependence in the rat. 117 53


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