Biomedical subjects

A Zaimovic

Publications and source records attributed to A Zaimovic.

41 records · Page 3Linked to original sources

PubMed1996

Intravenous flumazenil following prolonged exposure to lormetazepam in humans: lack of precipitated withdrawal.

The capacity of flumazenil to reverse benzodiazepine agonist effects has been widely demonstrated. In contrast, the role of flumazenil in precipitating withdrawal symptoms is unclear in humans: the inability of RO 15-1788 to induce benzodiazepine withdrawal seems to be related to the duration of exposure to the GABAergic drugs. In the present experiment we evaluated the effects of intravenous flumazenil or placebo in 36 healthy volunteers pretreated with lormetazepam for 30 days (2 mg/day) and 18 lormetazepam-dependent subjects (6-8 mg/day). Measurements of a balance task, subject- and observer-rated symptoms showed a reversal of lormetazepam effects induced by flumazenil without any significant withdrawal symptoms. Slight anxiety, increase in heart rate and perspiration were observed in a few subjects. Independent of benzodiazepine doses, long-term treatment seems to be responsible for tolerance development with consistent changes in GABA-benzodiazepine receptor sensitivity. Flumazenil could be able to normalize benzodiazepine receptor sensitivity and exert its weak agonist activity.

Adult↗

PubMed1995

Serotonin function in detoxified heroin abusers: prolactin and cortisol responses to fenfluramine challenge.

The function of the central serotonergic system was examined indirectly through the measurement of prolactin (PRL) and cortisol responses to fenfluramine challenges in 27 heroin addicts 2 months after detoxification and in nine healthy volunteers. Heroin abusers included nine addicts with comorbid depressive disorders (Group A), nine with aggressive behavior and antisocial personality (Group B), and nine with heroin addiction uncomplicated by other Axis I and II psychiatric disorders (Group C). PRL and cortisol responses of patients in Group A were blunted, while those of patients in Groups B and C did not differ from those of the healthy volunteers. Cortisol responses in Group A differed significantly from those in the other patient groups and in the normal comparison group for AUC analyses, but the diagnosis x time interaction showed a significant difference only between Group A and the normal group. Our data suggest that the function of the serotonergic system is impaired in heroin addicts with comorbid depression but not in heroin addicts who are not clinically depressed. Thus, the serotonergic system does not appear to be impaired by prolonged opioid exposure, per se.

Adult↗

PubMed1995

Hostility in heroin abusers subtypes: fluoxetine and naltrexone treatment.

1. Substance abusers subtypes have been identified considering underlying psychobiological disorder, familial factors, age of onset, legal problems and drug of choice. 2. In the present study the authors submitted 98 male heroin addicted individuals (age 19-28 y) to the Buss Durkee Hostility Inventory (Italian version) and a structured interview concerning social and clinical history; legal problems, age of onset of drug abuse, drug of choice. 3. Serotonergic system sensitivity was evaluated with fenfluramine challenge for PRL assay. 4. Thirty two patients (group A) showed high score for resentment and guilt at BDHI (hostility in), low rate of legal problems, late age of onset, preference for heroin and alcohol. Twenty nine patients (group B) showed high score for assault and irritability at BDHI (hostility out), high rate of legal problems, early age of onset, preference for heroin and cocaine. The other 37 patients (group C) showed aggression score in the normal range at BDHI, no legal problems, late onset of substance abuse, preference for heroin only. 5. PRL responses was blunted in group A (p < 0.001) and significantly decreased in group B (p < 0.05). PRL plasma levels were inversely correlated with HRSD scores. 6. All the patients were included in a treatment protocol with fluoxetine and naltrexone or placebo and naltrexone for 6 months. 7. The treatment was effective in group A with a significant improvement of BDHI results and decrease of craving score, lower level of drop out, lower level of positive urine controls. No significant differences between fluoxetine and placebo effects have been evidenced in patients of group B and C. The present findings suggest that psychopharmacological approach to addiction needs a diagnostic screening for specific subtypes.

Adult↗

PubMed1995

Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid.

Gamma-hydroxybutyric acid (GHB) has been recently used in alcohol detoxification, but conflicting data are available concerning the central mechanism of action of this GABA catabolite. GHB ability to stimulate growth hormone (GH) secretion has been reported. Our previous studies revealed the ability of flumazenil (a benzodiazepine antagonist) to counteract GHB effects on GH secretion. Other hypotheses, including an opioid or serotonergic role of GHB, have been considered. In the present study we investigated GH responses to GHB with or without naloxone (an opiate receptor antagonist) or metergoline (a serotonin receptor antagonist) pretreatment. This study included 10 male healthy volunteers (aged 24.3 +/- 2.9 years) who were submitted to four tests in random order: (A) oral GHB administration; (B) oral GHB and i.v. naloxone administration; (C) oral GHB and oral metergoline administration; and (D) oral placebo and i.v. saline administration. Blood samples for GH assay were collected during the three tests at -15, 0, 15, 30, 45, 60 and 90 min. GHB induced a significant increase in GH plasma levels; naloxone pretreatment did not antagonize GHB action on GH secretion; metergoline significantly decreased GH response to GHB (p < 0.05). No changes were obtained with placebo and saline administration. The opioid system does not seem to be involved in GHB effects on GH-secreting pituitary cells; GHB effects on the serotonergic system influencing GH secretion, on the other hand, cannot be excluded.

Adult↗

PubMed1994

Alpha-1- and 2-adrenoceptor subsensitivity in siblings of opioid addicts with personality disorders and depression.

Noradrenergic receptor sensitivity of 16 healthy male siblings of heroin addicts and of 8 age and sex-matched controls was examined by administering a clonidine stimulation test and by measuring the resulting growth hormone (GH) (alpha-2-adrenoceptors) and beta-endorphin (beta-endorphin) (alpha-1-adrenoceptors) responses. Siblings were divided into two groups: A = siblings of heroin addicts with personality disorders and high aggressivity and B = siblings of heroin addicts without mental disorders. The GH and beta-endorphin responses to clonidine were blunted in group A subjects compared with controls and normal in group B.

Adult↗