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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute opioid physical dependence refers to the withdrawal symptoms precipitated by an opioid antagonist administered after a single dose or short-term infusion of an opioid agonist. This phenomenon is particularly interesting given that the abstinence syndrome has generally been thought to develop only after chronic exposure to opioid agonists. The purpose of this study was to determine the minimum time after agonist administration when antagonist-precipitated withdrawal could be observed. Naloxone (10 mg/70 kg) was administered i.m. either 0, 15, 45 or 90 min after single i.m. injections of morphine (18 mg/70 kg) in five nondependent male opiate users. Physiological and subjective report measures revealed no effect of morphine or naloxone at the 0 and 15 min morphine-naloxone interval conditions; however, before the naloxone challenge 45 and 90 min post-morphine, agonist effects (e.g., miosis, respiratory depression and good drug effect subjective ratings) were clearly evident. Naloxone reversed these effects to premorphine levels and simultaneously precipitated subjective symptoms and observer rated signs of opiate withdrawal. Thus, this study showed that antagonist-precipitated withdrawal in humans was first observed 45 min after agonist administration. Further, the onset of naloxone-precipitated withdrawal effects closely paralleled the onset of morphine agonist effects. The results of this study suggest that adaptational changes underlying the development of physical dependence begin within minutes after acute exposure to an opiate.
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PMID:Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval. I. 276 Aug 39

Antagonist-precipitated withdrawal after acute opioid administration (acute physical dependence) is an interesting phenomenon in that the opioid abstinence syndrome is generally thought to develop only after prolonged exposure to opioid agonists. The purpose of this study was to examine further this phenomenon in humans by characterizing the antagonist dose-response function. The effects of i.m. naloxone (0, 0.1, 0.3, 1, 3, 10 and 30 mg/70 kg) were assessed 6 hr after single i.m. injections of morphine (18 or 30 mg/70 kg) in six subjects with a history of chronic opiate use. Naloxone reversed residual morphine effects, including miosis and respiratory depression. The degree of reversal was dose-related to 10 mg/70 kg of naloxone with no further increases at the highest naloxone dose. Simultaneously, observer ratings of withdrawal signs and subjective reports of withdrawal symptoms were increased in an orderly dose-related manner to 30 mg/70 kg of naloxone. Reversal of residual morphine effects and onset of precipitated withdrawal were evident by 5-min postnaloxone; peak effects occurred within 15 min. This study confirmed the occurrence of antagonist-precipitated withdrawal after brief opioid exposure in humans, demonstrated the rapid onset of withdrawal effects and characterized the naloxone dose-response function.
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PMID:Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure. 291 67

Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man. Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity. Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine, nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like (i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary dependence studies have demonstrated that physical dependence is possible at high dose levels that produce marked side effects. Other studies show that dependence is unlikely to be of significance within nalbuphine's usual analgesic range. Six-month studies in patients with chronic pain have confirmed that analgesic tolerance or physical dependence is uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nalbuphine. 298 29

Analgesics such as morphine are toxic drugs that kill by producing respiratory depression. Further morphine-like drugs produce a high level of physical dependence and are highly reinforcing in some subjects. A systematic search, conducted over the last 50 years, for safer and less addicting analgesic has revealed that opioid analgesics act on different types of opioid receptors (mu, kappa, and sigma), and that they may function as mixed agonist-antagonists or as partial agonists. Thus some mixed agonists function as competitive antagonists at the mu receptor and as partial or strong agonists at the kappa or sigma receptor. When mixed agonists produce the same pharmacologic effects (eg, analgesia) by acting on different receptors, they invoke the principle of receptor dualisms. Drugs that produce agonist (analgesic) effects by acting on the kappa receptors are an order of magnitude safer than the mu agonists and produce a lesser degree of physical dependence than strong mu agonists. Thus safer, less addicting analgesics have been produced that act either as agonist-antagonists or by being partial agonists.
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PMID:Clinical evidence for different narcotic receptors and relevance for the clinician. 301 58

A single intoxicating dose of chlordiazepoxide HCl (p.o.) in the rat can induce quantifiable manifestations of physical dependence. Dependence was revealed by antagonist precipitation (Ro 15-1788, CGS-8216) as well as spontaneous emergence of neurobehavioral signs of withdrawal observed by multiple raters blind to treatments. Ro 15-1788 was 45% more effective than CGS-8216 in both reversing chlordiazepoxide intoxication and expressing withdrawal signs. The severity of Ro 15-1788-precipitated withdrawal varied with chlordiazepoxide dose, Ro 15-1788 dose and the agonist-antagonist dose interval. Maximal precipitated dependence was evoked 3 days after chlordiazepoxide HCl (450 mg/kg) by Ro 15-1788 (25 mg/kg i.p.). The precipitated syndrome consisted of tail erection, reduced motor activity, high step, curled claw, arched back, muscle hypertonus and piloerection. Ro 15-1788-precipitated dependence emerged between 28 and 52 hr, peaked at 76 hr and disappeared by 124 hr. Spontaneous withdrawal had emerged from 100 to 124 hr and then faded gradually. The neurobehavioral expression of central nervous system depression and its reversal were necessary but not sufficient conditions for the induction and expression of acute chlordiazepoxide dependence. These results suggest caution in reviving acute benzodiazepine-overdosed patients to avoid iatrogenic withdrawal analogous to naloxone for opiates.
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PMID:Pharmacologic characterization of acute chlordiazepoxide dependence in the rat. 309 61

The study concerns the use of a new antidepressant, tianeptine, as a treatment of depressive and/or amotival syndrome, in 30 drug addicts, detoxified from opiates. From a thymoanaleptic point of view, 85% of the patients exhibit a positive result after 28 days of treatment with 37.5 mg/day. These good results are confirmed by the evolution of the Hamilton Depression Rating Scale global score, which significantly decreases from D0 to D14 and from D14 to D28. The acceptability of the antidepressant is good. Anticholinergic side-effects are very uncommon. Tianeptine appears devoid of any obvious psychostimulant or sedative effect. The drug compliance, estimated by counting the tablets, is very satisfying: there is no tendency to a spontaneous increase of dosing. The follow-up of the patients after drug cessation has not shown any symptoms suggesting psychological or physical dependence towards the drug. During this study in subjects particularly predisposed to the abuse of psychoactive drugs, tianeptine has not induced anything suggesting the possibility of drug abuse or tolerance.
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PMID:[Treatment with tianeptine of depressive disorders in drug addicts under withdrawal. Assessment of efficacy and study of dependence]. 332 2

This study assessed the effects of i.m. naloxone (10 mg) 6 hr after acute i.m. injections of morphine (0, 1, 3, 5.6, 10 and 17 mg). Naloxone reversed residual morphine-produced respiratory depression, miosis and subjective reports of drug "high." In addition, naloxone precipitated signs and symptoms characteristic of opioid withdrawal. Subjective report measures of "bad" drug effects and specific opioid withdrawal symptoms increased as a function of morphine pretreatment dose, as did observer-rated signs of withdrawal. Yawning was the most prominent observed sign, whereas yawning and irritability were the most consistently reported subjective symptoms. Peak withdrawal effects were seen within 15 min post-naloxone. The results of this study confirm previous reports of acute physical dependence in man and extend those findings by demonstrating a morphine dose-response function.
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PMID:Acute physical dependence in man: effects of naloxone after brief morphine exposure. 333 95

Aniracetam, 1-p-anisoyl-2-pyrrolidinone, is known to be a nootropic or cognitive activator. Aniracetam protects against memory and learning deficits without causing effects on motor function and the autonomic nervous system. A drug dependence study on aniracetam utilizing the intragastric route of administration was performed in male cynomolgus monkeys. The behavioral observation test after acute administration revealed that aniracetam at the dose of 25-400 mg/kg did not change the gross behavior. In the self-administration initiation test, animals were exposed to two or three unit doses of aniracetam and references for a total available period of 7 weeks. Aniracetam at the dose of 25, 50 and 75 mg/kg/injection did not initiate self-administration in the respective group of 4, 4 and 2 animals. In the study with d-methamphetamine hydrochloride at the dose of 0.1 mg/kg/injection, 1 out of 4 animals started to consistently self-administer the drug. Self-administration of cocaine hydrochloride at the dose of 10 mg/kg/injection was confirmed in 3 out of 5 animals, and these 3 animals died from overdosing later. In the physical dependence direct induction test, animals received aniracetam (50 mg/kg) and sodium pentobarbital (25 mg/kg: the dose inducing intermediate CNS depression) intragastrically twice a day for 31 consecutive days. Abrupt withdrawal of aniracetam did not elicit abstinent signs (including changes in appetite and body weight) in all 6 animals, whereas withdrawal of pentobarbital produced typical abstinent behavioral signs and decreases in appetite and body weight. In conclusion, aniracetam was confirmed to develop neither physical dependence nor psychic dependence in cynomolgus monkeys.
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PMID:[Drug dependence test on a cerebral insufficiency improver, aniracetam]. 357 Jan 3

An acute administration of MCI-2016 at the doses of 30, 100 and 300 mg/kg (p.o.), and 10, 20 and 30 mg/kg (i.p.) produced a slight CNS depression in rats, such as, sedation, ptosis, decrease in motor activity and systemic muscle relaxation. In a direct physical dependence test, rats were fed the MCI-2016-admixed food together with drinking water ad libitum for 24 hours daily for 51-71 days (mean MCI-2016 intake 29.9-210.7 mg/kg/day), on the gradedly increased dosage schedule with a dosage level of 0.25 and 0.5 mg/g food to 4 mg/g food. In a natural withdrawal following administration of MCI-2016, no significant withdrawal signs were observed in any group. In a naloxone-precipitation test the rats that were treated with MCI-2016-admixed food did not show any withdrawal signs. In a substitution test in either morphine or barbital dependent rats, no suppression of withdrawal signs or maintenance of dependence were observed by cross-administration of MCI-2016. In conclusion, MCI-2016 was considered to have no physical dependence potential.
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PMID:[Physical dependence liability test of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) in rats]. 362 10

Adenosine triphosphate (ATP) injected intravenously in mice was found to have dose-dependent analgesic activity in the hot plate and phenylquinone-induced stretching assays. ATP prolonged the hot plate latency (ED50 value of 1 (0.7-1.4) mg/kg) and inhibited phenylquinone-induced writhing (ED50 value of 0.4 (0.31-0.52) mg/kg). Low doses of ATP produced a potent antinociceptive effect without any significant depression of locomotor activity. Treatment of mice for either 4 days or 14 days with ATP did not result in development of physical dependence on or tolerance to ATP. The analgesic action of ATP was not antagonized by naloxone at 1 and 5 mg/kg. ATP analgesia was antagonized, in a dose-related fashion, by Ca++ ion injected intracerbroventricularly which may indicate that Ca++ plays a role in ATP-induced antinociception.
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PMID:Characteristics of analgesia induced by adenosine triphosphate. 368 52


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