Opioid-like adverse effects of tianeptine in male rats and mice.

RATIONALE: Tianeptine is a mu-opioid receptor (MOR) agonist with increasing reports of abuse in human populations. Preclinical data regarding the abuse potential and other opioid-like adverse effects of tianeptine at supratherapeutic doses are sparse. OBJECTIVES: The present study evaluated tianeptine in a rat model of abuse potential assessment and in mouse models of motor, gastrointestinal, and respiratory adverse effects. METHODS: Abuse potential was assessed in adult male Sprague-Dawley rats using an intracranial self-stimulation (ICSS) procedure to determine effects of acute and repeated tianeptine on responding for electrical brain stimulation. Male ICR mice were used to determine the effects of tianeptine in assays of locomotor behavior and gastrointestinal motility. Male Swiss-Webster mice were monitored for respiratory changes using whole-body plethysmography. RESULTS: In rats, acute tianeptine produced weak and delayed evidence for abuse-related ICSS facilitation at an intermediate dose (10 mg/kg, IP) and pronounced, naltrexone-preventable ICSS depression at a higher dose (32 mg/kg, IP). Repeated 7-day tianeptine (10 and 32 mg/kg/day, IP) produced no increase in abuse-related ICSS facilitation, only modest tolerance to ICSS depression, and no evidence of physical dependence. In mice, tianeptine produced dose-dependent, naltrexone-preventable locomotor activation. Tianeptine (100 mg/kg, SC) also significantly inhibited gastrointestinal motility and produced naloxone-reversible respiratory depression. CONCLUSIONS: Tianeptine presents as a MOR agonist with resistance to tolerance and dependence in our ICSS assay in rats, and it has lower abuse potential by this metric than many commonly abused opioids. Nonetheless, tianeptine produces MOR agonist-like acute adverse effects that include motor impairment, constipation, and respiratory depression.

Performance evaluation of four on-site drug-testing devices for detection of drugs of abuse in urine.

On-site drug tests are becoming increasingly more popular because of their easy test protocols and instantaneous results. This study evaluates the performance of four on-site drug testing devices that use competitive binding immunoassays to qualitatively determine the presence of drugs in urine: Triage Panel for Drugs of Abuse plus TCA, QuickScreen Pro-Multi Drug Screening Tests, Syva Rapid Test d.a.u. 5 and d.a.u. 2, and Rapid Drug Screen. All devices simultaneously determine the presence of the following drugs of abuse: amphetamine (AMP), benzoylecgonine (BE), 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCA), opiates (OPI), and phencyclidine (PCP). Triage and Rapid Drug Screen also simultaneously test for benzodiazepines (BZB) and barbiturates (BRB), whereas QuickScreen and Rapid Test require separate devices for the BZB and BRB analyses. Urine specimens (222) containing drug concentrations around or above cutoff values were screened by ONLINE or EMIT II immunoassays. Of these, 199 yielded positive gas chromatography-mass spectrometry results with at least 17 positive specimens in each drug class. Specimens with the target drugs added at 16.7% above and below the cutoff, 33.3% above and below the cutoff, and 66.7% above the cutoff were also used to evaluate the test devices. Sensitivity and specificity calculations demonstrated that Triage performed most predictably in the donor urine specimens and the drug-added specimens. In addition, it required the least amount of test volume and was the only device in which the appearance of a colored line indicated a positive result. Therefore, of the devices studied, Triage was the most dependable and reproducible on-site drug-screening device.