Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of NG-monomethyl-L-arginine (NMMA), an inhibitor of nitric oxide synthase (NOS), on the development of tolerance to and physical dependence on morphine was determined in the rat. 2. Male Sprague-Dawley rats were rendered tolerant to and dependent on morphine by the subcutaneous implantation of four morphine pellets (each containing 75 mg morphine base) during a 3 day period. Placebo pellet implanted rats served as controls. 3. Chronic administration of morphine resulted in the development of tolerance to the analgesic action of morphine. Twice daily injections of NMMA (4 or 8 mg/kg) attenuated the tolerance to morphine as evidenced by higher analgesic response in NMMA treated than in vehicle treated morphine tolerant rats. 4. Chronic administration of morphine also resulted in the development of physical dependence as evidenced by the appearance of a variety of symptoms including stereotyped jumping response following naltrexone injection. Concurrent treatment with NMMA inhibited naltrexone-induced jumping response but other responses like fecal boli formation, wet dog shakes, teeth chattering, rearing and ejaculations were not modified. 5. It is concluded that inhibition of NOS can attenuate the development of tolerance to, and physical dependence on, morphine in the rat. However, it appears that higher doses of NOS inhibitors are required in the rat than in the mouse for blockade of both tolerance and physical dependence processes.
Gen Pharmacol 1995 Sep
PMID:Attenuation of tolerance to, and physical dependence on, morphine in the rat by inhibition of nitric oxide synthase. 755 49

1. In previous studies, we have demonstrated that delta-opioid receptors are involved both in the acute control of hypothalamus-pituitary-adrenocortical (HPA) axis activity and in the development of neuroendocrine opioid tolerance. In the present work we studied whether central delta-opioid receptors play a role in the development of neuroendocrine physical dependence to opioids in the rat. 2. Intracerebroventricular (i.c.v.) administration of the delta-selective agonist DPDPE ([D-Pen2,D-Pen2]enkephalin) produced stimulation of HPA activity, as shown by an increase in corticosterone release. This effect was antagonized by i.c.v. co-administration of ICI 174,864, a selective delta-receptor antagonist, which provide direct evidence that the activation of the HPA axis produced by DPDPE is mediated by central delta-opioid receptor. 3. Chronic pretreatment with i.c.v. DPDPE resulted in tolerance to its neuroendocrine effect. Intracerebroventricular injection of ICI 174,864 to DPDPE-tolerant rats produced neither alteration in corticosterone release nor behaviour signs of dependence. 4. It was concluded that delta-opioid receptors do not play a role in the development of opioid neuroendocrine physical dependence at the HPA axis.
Gen Pharmacol 1994 Jul
PMID:Lack of involvement of delta-opioid receptor in mediating physical dependence at the hypothalamus-pituitary-adrenocortical (HPA) axis in the rat. 795 33

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.
Gen Pharmacol 1994 Jan
PMID:Effects of naltrexone pellet implantation on morphine tolerance and physical dependence in the rat. 802

1. The time course of the effect of chronic administration of morphine on the activity of nitric oxide synthase (NOS) in the brain regions and spinal cord of the mouse was determined. The effect of naltrexone by itself on the NOS activity and that induced by morphine also were determined. 2. Male Swiss Webster mice were implanted subcutaneously with a pellet containing 25 mg of morphine free base for 4 days. Placebo pellet implanted mice served as controls. 3. Twenty-four hours after treatment with morphine, NOS activity decreased in the cerebellum, midbrain, cortex and remainder of the brain as well as in the spinal cord. Forty-eight and 72 hr after the treatment with morphine, NOS activity increased in the cerebellum and cortex, but no change was observed in the other brain regions and spinal cord. Twenty-four hours after morphine pellet removal (withdrawal), NOS activity in all brain regions and the spinal cord has returned to normal. 4. Implantation of a pellet containing 10 mg of naltrexone did not alter NOS activity in any brain region or spinal cord for 24, 48 and 72 hr or 24 hr after removal of the pellet. 5. Implantation of a naltrexone pellet in conjunction with a morphine pellet blocked the changes in NOS activity in the brain region and spinal cord induced by morphine. 6. It is concluded that the initial decrease in NOS activity by morphine may be related to enhanced motor activity, whereas the increase in NOS activity in certain brain regions may be associated with tolerance-physical dependence development. Additionally, the changes in central NOS activity by morphine appear to be mediated by opioid receptors because they were blocked by concurrent treatment with naltrexone.
Gen Pharmacol 1997 Aug
PMID:Time course of the changes in central nitric oxide synthase activity following chronic treatment with morphine in the mouse: reversal by naltrexone. 925 3

Opioids have been used for thousands of years for pain relief. Transdermal fentanyl (TDF) is a synthetic opioid that is prescribed for the treatment of chronic pain. This clinical lesson demonstrates that TDF may be easy to start but sometimes difficult to stop. Like any other opioid there is a substantial risk of physical dependence and subsequent withdrawal symptoms after discontinuation of the drug. Here, we present a case of a hospice patient who developed withdrawal symptoms after a first TDF tapering attempt according to the manufacturer's instructions. A second, more gradual tapering regimen did not result in withdrawal symptoms. The mechanisms and treatment modalities for physical dependence along with a tailor-made tapering strategy that is suitable for general practice are presented in this clinical lesson.
Eur J Gen Pract 2011 Dec
PMID:Disaster after the plaster. Fentanyl withdrawal symptoms in a curable hospice patient. 2187 7


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