Effects of maprotiline, nomifensine and Trazodone on gamma amino butyric acid turnover in the limbic system

The effects of chronic treatment with 3 antidepressant drugs: Maprotilline, Nomifensine and Trazodone on the turnover rate of gamma amino butyric acid were studied in 4 rat brain areas related to the limbic system. Trazodone markedly increased the Gamma amino butyric acid level in the hypothalamus and hippocampus but lowered its level in the amygdala and olfactory tubercle. Nomifesine increased its level in the hypothalamus and hippocampus and markedly decreased it in the olfactory tubercle. Maprotilline on the other hand consistently lowered its level in all 4 areas. These results indicate the involvement of gamma amino butyric acid in the mechanism of action of antidepressant drugs. Its possible role in modulating other neurotransmltters and production of antidepressant manifestations are discussed

Effects of maprotiline, nomifensine, and trazodone on monoamine turnover in the limbic system

The effects of 14-day treatment of three antidepressant drugs [maprotiline, nomifensine, and trazodone] was studied on the turnover of norepinephrine, dopamine and serotonin in 4 limbic areas of rat brain hypothalamus, hippocampus, amygdala and olfactory tubercle. The monoamine metabolites accumulated in those brain areas were analyzed by HPLC method. The 3 drugs produced significant increase in the level of norepinephrine metabolite [MHPC] in the hypothalamus and hippocampus, nomifensine increased its level also in the olfactory tubercle. In the amygdala, maprotiline significantly decreased while the two other drugs slightly increased the MHPG level on the Dopamine metabolite [HVA]. Nomifensine significantly increased its level in the hippocampus, hypothalamus and the olfactory tubercle and trazodone produced the highest increase in the amygdala. On serotonin metabolite [5-HIAA] trazodone produced marked increase of its level in the hypothalamus, hippocampus and amygdala and maprotiline markedly increased its level in the amygdala. The results indicated that the primary action of maprotiline is to enhance norepinephrine turnover, while nomifensine markedly increased turnover of both norepinephrine and dopamine and trazodone markedly increased turnover of serotonin and norepinephrine

Neuromuscular and clinical effects of a new non depolarizing muscle relaxant [mivacurium chloride] during nitrous oxide fentanyl and nitrous oxide-isoflurane anesthesia

The neuromuscular and clinical effects of mivacurium chloride were studied during nitrous oxide-oxygen-fentanyl [BAL group n = 54] or nitrous oxide-oxygen-isoflurane [ISO group n = 54] anesthesia in adult surgical patients who received mivacurium either as a single bolus dose, repeated bolus doses, or an infusion. Neuromuscular response was evaluated by recording the force of contraction of the adductor of the thumb during train of four stimulations at 0.1 Hz. Mivacurium produced a dose-dependent neuromuscular block in each group. The dose response curve for the ISO group was significantly shifted to the left of that for the BAL group. The estimated ED 50 and ED 95 were 0.42 mg/kg and 0.074 mg/kg for the BAL group and 0.029 mg/kg and 0.05 mg/kg for the ISO group. Infusion rates averaged 7.5 ug/kg/min. in the BAL group and 5.4 ug/kg/min. in the ISO group. Plasma concentration of mivacurium at the end of infusion averaged 206 ng/ml for the BAL group and 171 ng/ml for the ISO group. The recovery indices [T 25 - T 75] for initial bolus dose, repeated bolus doses, and mivacurium infusion were not significantly different in each anesthetic group. There were no significantly hemodynamic changes in groups given mivacurium doses up to and including 2 x ED 95 by bolus i.v. administration

Evaluation of long term use of amiodarone in low dose

Thirty two patients with ventricular or supraventricular arrhythmias were treated with amiodarone in low dose [1000 mg/week] for more than 6 months. Amiodarone serum level as well as the level of its metabolite desethylamiodarone was determined biweekly using an HPLC method. Serum levels attained were around the lower end of the therapeutic range. Significant variation in serum level was observed within the same patient over time scale. The low dose used did not produce major side effects but was highly effective in controlling the arrhythmia. The effect on ECG intervals was studied during the steady state period of the drug. The PR interval was prolonged without leading to heart block. The QT interval showed an increase of a mean value of 16% +8.4%. Significant correlation was found between prolongation in ECG intervals and the drug serum level. This correlation was more significant with the metabolite desethylamiodarone than with the parent compound amiodarone. Arrhythmia whether supraventricular or ventricular was controlled in all patients [100%]. It is concluded that low dose amiodarone is highly effective in controlling supraventricular and ventricular arrhythmias with no major side effects

Efficacy of intravenous amiodarone in treatment of arrhythmia after adult cardiac surgery

The response of cardiac arrhythmias to amiodarone therapy was studied in 58 cardiac surgery patients with pre or post-operative arrhythmia. Patients were given amiodarone intravenously in a dose of: 5 mg/kg body weight followed by 400 mg. orally after 2 hours. The serum amiodarone and its metabolite, desethylamiodarone were monitored every two hours. The time at which reversion to sinus rhythm occurred was recorded in each patient. About 46 percent of patients with postoperative atrial arrhythmia reverted within the first 2 hrs, and 20 percent reverted at 4 hrs, after amiodarone administration. While in patients with preoperative atrial arrhythmias only 18 percent reverted at 2 hrs, and 32 percent at 4 hrs. Cases with ventricular arrhythmias, although few, still show a longer delay in response to the amiodarone treatment. The earlier response of cases with postoperative atrial arrhythmias could be correlated to serum amiodarone level, the more established preoperative arrhythmias conceivably required longer time to respond. Apart from, mild hypertension, nausea, tremors and headache, no life threatening toxic manifestation has occurred with the present amiodarone regimen

Effect of carbamazepine and phenyton on clonazepam and 7 amino clonazepam serum level

The effect of carbamazepine and phenytoin on the serum level of clonazepam and its major metabolite 7-aminoclonazepam was studied in epileptic patients chronically treated with combination of those drugs. Carbamazepine produced consistent but insignificant lowering of the clonazepam serum level which averaged 20% without noticeable effect on the 7-aminoclonazepam. Phenytoin, however, produced significant reductions in clonazepam with slight lowering of 7-aminoclonazepam. The present finding indicated that phenytoin and, to less extent, carbamazepine lower the clonazepam serum level. The finding also suggested that the effect may be due to enhanced metabolism of clonazepam via transformation into 7-aminoclonazepam

Efficacy of intravenous amiodarone in treatment of arrhythmia after adult cardiac surgery

The response of cardiac arrhythmias to amidoarone therapy was studies in 58 cardiac surgery patients with pre or post-operative arrhythmia. Patients were given amidoarone intravenously in a dose of:5mg/kg do by weight followed by 400mg. orally after2 hours. The serum amidoarone and its metabolite, desethylamiodarone were monitored every two hours. The time at which reversion to sinus rhythm occurred was recorded in each patient. About 46% of patients with postoperative atrial arrhythmia reverted within the first 2 hrs, and 20% reverted at4 hrs, after amidoarone administration. While inpatients with postoperative atrial arrhythmias only 18%reverted at 2 hrs, and32% at 4 hrs. cases with ventricular arrhythmias, although few, still show a longer delay in response to the amidoarone treatment. The earlier response of cases with postoperative atrial arrhythmias could be correlated to serum amidoarone level, the more established preoperative arrhythmias conceivable required longer time to respond. Apart from, mild hypotension, nausea, tremors and headache, no lift-threatening toxic manifestation has occurred with the present amidoarone regimen