No abstract

The higher increase of the metabolites as compared with the parent compounds can be explained by a paroxetine-induced inhibition of the liver enzyme cytochrome P4502D6, which catalyses the second step of the TCA metabolism, i.e. the hydroxylation of the metabolites. Blood levels should be meticulously monitored, if TCAs are combined with paroxetine.

A double-blind multicenter randomized parallel group study comparing paroxetine and maprotiline was carried out in a total of 544 outpatients. Included were patients with varying degrees of severity of depressive symptoms who fulfilled modified RDC criteria for either Minor or Major Depression and showed a HAMD-17 score of > or = 13. No concomitant benzodiazepine treatment was allowed. Duration of treatment was 6 weeks, after an initial wash-out period. Doses were fixed during the first 3 weeks of treatment, patients receiving either 20 mg paroxetine or 100 mg maprotiline daily. An option for dose escalation was provided for insufficient responders after 3 weeks. The weekly assessments comprised rating of the HAMD-17, MADRS, BRMS, RDS, HAMA, CAS, and CGI scales and registration of adverse events by non-leading questions. An intention-to-treat and a completer analysis were performed. Response was defined as a HAMD-17 reduction of > or = 50% or a HAMD-17 score of < or = 9 at the end of the study or at dropout. The treatment groups were comparable according to demographic data. Overall evaluation indicated equieffective and good antidepressant and anxiety-reducing properties for paroxetine and maprotiline. No persistent significant differences between treatment groups were observed on any assessment instrument. There was no difference in the frequency of observed side-effects, but side-effect profiles were markedly different, as maprotiline patients had more anticholinergic and paroxetine patients more SSRI-typical side-effects.

The effect of treadmill physical training (PT) on rat gastrocnemius/plantaris muscle after bilateral femoral artery ligation was investigated. To enable a comparison to be made between the susceptibility of muscles with restricted blood flow and normally perfused skeletal muscle to PT, animals without ligated femoral arteries also underwent PT. PT increased the oxidative capacity of the gastrocnemius/plantaris muscle, as judged by the activity of citrate synthase, and reduced muscle fatigue in both groups of animals. Exercise also tended to lower the activity of a marker enzyme for glycolysis, glyceraldehyde-phosphate dehydrogenase in all animals, although this only reached the level of statistical significance in the animals with ligated femoral arteries. In the animals with restricted muscle blood flow, PT increased gastrocnemius skeletal muscle blood flow and pO2 and prolonged the time taken to attain maximum muscle twitch tension. The results indicate a great susceptibility of hindlimb skeletal muscles of rats with ligated femoral arteries to PT. They also suggest that the beneficial effect of PT observed in man with chronic occlusive arterial disease (COAD) may result both from an increase in muscle blood flow and from an enhanced mitochondrial respiratory activity in the afflicted muscle.

Denbufylline (1,3-di-n-butyl-7-[2-oxopropyl]-xanthine) has been examined in passive avoidance trials in gerbils, following transient forebrain ischaemia, and in mice. Animals were conditioned to avoid a darkened compartment by means of a foot shock received upon entering. Learning and memory were tested 24 hr later by replacing the animals in the box and measuring the latency to enter the dark compartment. In gerbils, transient (5 min) forebrain ischaemia was induced 24 hr prior to training by bilateral closure of the carotid arteries. Controls were sham-ligated. All gerbils received seven subcutaneous injections of saline or denbufylline, the first during forebrain ischaemia or immediately following sham-ligation, and the rest 3, 6, 24, 27, 30, and 48 hr later. Mice received one subcutaneous injection of saline or denbufylline immediately after training. The results show that denbufylline enhances memory formation in mice after a mild learning stimulus and recollection in gerbils following forebrain ischaemia.