AbstractSterically hindered substrates can be employed in an enantioselective palladium‐catalyzed α‐arylation with the chiral monophosphorus ligand BI‐DIME. This process enabled an efficient synthesis of the antidepressant (S)‐nafenodone, a four‐step enantioselective synthesis of the Sceletium alkaloid (+)‐sceletium A‐4, a concise five‐step enantioselective synthesis of (−)‐corynoline, as well as a three‐step preparation of (−)‐DeN‐corynoline.

01 Jan 1999·NeuropsychobiologyQ4 · PSYCHOLOGY

Effect of Two Antidepressant Drugs on REM Sleep and EMG Activity during Sleep

Q4 · PSYCHOLOGY

Article

Author: Schulz, Hartmut ; Jahnig, Peter ; Jobert, Marc

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.

01 May 1996·Human Psychopharmacology: Clinical and Experimental

Effects of single and multiple doses of dexnafenodone, imipramine and placebo on sleep of young healthy volunteers

Author: H. Schulz ; U. Legler ; G. Greger ; M. Jobert

The effects on polygraphically recorded sleep of single and repeated doses of dexnafenodone (20 mg daily) were determined in 12 young, healthy subjects, and compared to those of imipramine (75 mg daily: six subjects) and placebo (six subjects).After two adaptation nights, sleep was recorded at baseline (night (0)), and after the first (night (1)) and last (night (5)) evening administration of the study drugs.REM sleep was substantially inhibited in both nights under the two active treatments, whereby the effect appeared immediately.With the exception of slow wave sleep (SWS), which was more reduced in night 1 under imipramine that under dexnafenodone, the other sleep stages were essentially unchanged.Time awake during bed rest increased under both active treatments, with a more rapid increase under dexnafenodone.Dexnafenodone, a potent inhibitor of noradrenaline, and to a lesser degree of serotonin reuptake, induced changes in the pattern of sleep which are comparable to those of non-sedating tricyclic antidepressants.The mode of action as well as the pharmacodynamic profile of dexnafenodone led to the expectation that this new substance will show antidepressive activity on a clin. level.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 1	-	AbbVie, Inc.	-

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