tp-7 and Substance-Withdrawal-Syndrome

Activity of a peptide tuftsin analogue Selank was studied in outbred rats using the naloxone-precipitated morphine withdrawal model. Single intraperitoneal injection of Selank in an anxiolytic dose of 0.3 mg/kg reduced the total index of morphine withdrawal syndrome by 39.6%, significantly (р<0.0001) attenuated convulsive reactions, ptosis, and posture disorders, and 9-fold increased the tactile sensitivity threshold in morphine-dependent rats in comparison with the group of active control; at the same time, Selank was slightly inferior to diazepam in a dose of 2 mg/kg by pharmacological activity (the decrease in total index of morphine withdrawal syndrome by 49.3% and 13-fold increase in sensitivity threshold). Thus, Selank, like diazepam, weakens the aversive signs of morphine withdrawal in rats with opiate dependence.

Topics: Animals; Diazepam; Morphine; Morphine Dependence; Naloxone; Rats; Substance Withdrawal Syndrome; Tuftsin

There are many nonopioid central nervous system depressant substances that share a gamma-aminobutyric acid (GABA) receptor-related mechanism of action. These sedatives-hypnotics can be indicated to treat anxiety, seizures, depression, and insomnia but are also used as substances of abuse and used to facilitate sexual assault. Barbiturates, methaqualone, and glutethimide were among the first type A GABA receptor-mediated sedative-hypnotics. Their clinical use was limited for most indications by serious adverse events and strong abuse potential but continue to be used illicitly around the world. The benzodiazepines supplanted barbiturates for most indications because they were less likely to cause severe adverse events in monotherapy. Flunitrazepam is a newer benzodiazepine that is preferentially used recreationally and to facilitate sexual assault. Flunitrazepam has greater potency and higher affinity for the type A GABA receptor than most benzodiazepines. Gamma-hydroxybutyric acid is sought illicitly for its hypnotic, euphoric and anabolic effects as well as to facilitate sexual assault. When any of these GABAergic drugs are used in high doses or with other sedative hypnotic agents, respiratory depression, coma, and death have occurred. Chronic use of these GABAergic drugs can lead to significant withdrawal syndromes. Phenibut and selank are poorly studied Russian drugs with GABAergic mechanisms that are inexplicably sold to US consumers as dietary supplements. Poison control center calls regarding phenibut have increased substantially over the past 5 years. Desired euphoriant effects account for the recreational and illicit use of many GABA-modulating agents. However, illicit use can lead to significant toxicities related to abuse, dependence, and subsequent withdrawal syndromes. Significant evaluation of developing agents with GABA properties should be conducted to determine abuse potential before public access ensues.

Topics: Drug Overdose; Flunitrazepam; gamma-Aminobutyric Acid; Humans; Hypnotics and Sedatives; Oligopeptides; Receptors, GABA; Receptors, Metabotropic Glutamate; Substance Withdrawal Syndrome; Substance-Related Disorders

We studied the effects of selank on the development of symptoms of acute 48-h alcohol withdrawal in outbred rats drinking 10 % ethanol as the only source of fluid for 24 weeks. In alcohol-preferring animals (mean daily ethanol intake >5.0 g/kg) allowed free choice between 10 % ethanol and water, single intraperitoneal injection of selank in a dose of 0.3 mg/kg eliminated anxiety induced by ethanol withdrawal in tests elevated plus maze and social interaction tests and prevented the formation of mechanical allodynia without affecting ethanol consumption. The fi ndings suggest that selank is effective in eliminating of alcohol withdrawal symptoms in rats.

Topics: Alcoholism; Animals; Animals, Outbred Strains; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Disease Models, Animal; Ethanol; Hyperalgesia; Injections, Intraperitoneal; Male; Maze Learning; Oligopeptides; Rats; Substance Withdrawal Syndrome; Treatment Outcome