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

The effect of D-Phenylalanine (D-Phe), putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in incubation mixture (up to 10(-3) mol/l) the hydrolysis of exogenous 3H-Met5-and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that that pharmacological activity of D-Phe is not directly related to the endogenous opiate system.
Pol J Pharmacol Pharm
PMID:The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. 376 85

Zolpidem, a new short-acting non benzodiazepine hypnotic with high selectivity for benzodiazepine--1/Omega-I receptors and with lack of tolerance and physical dependence in animal models and lack of withdrawal phenomena even after up to 180 days treatment has recently been introduced. Data from clinical trials show a comparable effectiveness in inducing and maintaining sleep to comparative drugs (benzodiazepines) and besides that, it seems to preserve--even improve sleep-architecture and lastly preserve daytime wakefulness. Very few studies have been conducted in psychiatric patients, but also in this group effectiveness has been shown, and from daily clinical experience, this picture seems to hold. It must be remembered, that psychiatric patients have a high level of symptomatic benzodiazepine and/or alcohol misuse disposing to withdrawal and abstinence states in which zolpidem is less effective presumedly reflecting its selectivity. Having passed the withdrawal states, zolpidem can be used as an effective and safe hypnotic.
Pol J Pharmacol
PMID:Zolpidem: clinical experience in psychiatric settings. 789 39

The effects of calcium channel inhibitors on ethanol intake and dependence in Wistar rats were studied. Nifedipine and isradipine were suspended in 1% Tween 40 saline solution and administered ip 60 min prior to testing. Audiogenic seizure response evaluation was performed after 5 days of ethanol treatment. Both nifedipine and isradipine significantly reduced the intensity score of convulsions and, in doses of 2.5 and 5.0 mg/kg, respectively, abolished them. Both drugs significantly reduced ethanol preference and intake in the high preference group of animals. Our results support the observations that certain dihydropyridine derivatives are capable of attenuating both ethanol preference and physical dependence.
Pol J Pharmacol
PMID:Comparative study of nifedipine and isradipine in animal models of ethanol dependence. 811 82