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)

The general pharmacological profile of levodropropizine (S(-)3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), a new antitussive drug, was compared with that of dropropizine racemate. Levodropropizine had weaker central sedative effects than the racemate and it did not induce physical dependence in rats. When given intravenously or intraperitoneally, levodropropizine did not exert any significant effects on the cardiovascular and respiratory systems. Receptor binding data excluded interaction with beta-adrenergic, muscarinic and opiate receptors. On the contrary, levodropropizine has affinity for H1-histaminic and alpha-adrenergic receptors. The affinity was also confirmed with isolated organ preparations. On the basis of this study, levodropropizine appears to have a better tolerability index than the racemate.
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PMID:General pharmacology of the new antitussive levodropropizine. 319 8

Male hooded rats were implanted with intravenous (IV) cannulas and housed in operant chambers. The effectiveness of two infusion schedules for producing physical dependence upon ethanol was assessed. Twenty-three rats (12 ethanol, 11 control) were tested under a 4 hr interinfusion schedule (one infusion every 4 hr, around the clock), and 29 rats (15 ethanol, 14 control) were tested under a 2 hr interinfusion schedule. During the dependence induction phase, which lasted for 6 days, the experimental rats received ethanol (30% v/v) at an average daily dose which ranged from 8.4-11.8 g/kg, and the dose administered per infusion was adjusted according to the degree of intoxication of each animal. The pair-fed control subjects received infusions of isocaloric control solutions (either 29% v/v propylene glycol or 31% v/v glycerol). Following the dependence induction phase, ethanol was withdrawn, and withdrawal symptoms were assessed. Blood ethanol levels (BEL) and signs of intoxication were determined through all phases of the experiment. During the dependence induction phase, mortality was close to zero, and weight loss was held to about 10%. Tolerance to ethanol developed in all experimental rats. During the withdrawal period, all ethanol rats developed clear withdrawal symptoms, while control subjects did not. Ethanol elimination rates ranged between 45-50 mg/dl/hr and withdrawal symptoms began when BEL fell below 200 mg/dl, and were severe when BEL approached zero. The 2 hr schedule proved superior to the 4 hr schedule in that it led to greater stability of BEL during dependence induction, and a tendency for the withdrawal reaction to be more severe.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of two intravenous infusion schedules for inducing physical dependence upon ethanol in rat. 654 15