Is Phosphodiesterase inhibition a new mechanism of antidepressant action?

Abstract

Unlike conventional antidepressants, rolipram (a new approach in the treatment of depression) stimulates both the presynaptic and the postsynaptic component of monoaminergic transmission. Several double blind trials are under way to assess the clinical efficacy and safety of this compound. The present study was a randomized, 4-week interindividual double blind double-dummy comparison with desipramine in inpatients with major (DSM-III) and/or endogenous (ICD-9) depressions. After a minimum washout period of three days the patients received either 0.50 mg rolipram or 25 mg desipramine orally t.i.d. for the first three days, then 0.75 mg rolipram or 50 mg desipramine t.i.d. until day 28. Rating tests were based principally on the AMDP-system and the HAMD scale. The study showed no differences between the two drugs as regards the efficacy, but a definite trend in favour of rolipram as regards the side effects and, in particular, anticholinergic effects.

The Phosphodiesterase Type 4 Inhibitor, Rolipram, Enhances Glucocorticoid Receptor Function

“…One PDE type 4 inhibitor, rolipram, has been shown to have antidepressant effects (Zhu et al 2001;Bobon et al 1988, Eckmann et al 1988. Rolipram was first demonstrated to have potent antidepressant activity in animal models (Zhu et al 2001;Wachtel and Schneider 1986).…”

“…The PDE isozyme type 4 is specific for cAMP and is expressed throughout the brain and immune system (Perez-Torres et al 2000;Engels et al 1994). Thus, inhibitors of PDE type 4 provide a pharmacologic strategy to increase prevailing cAMP levels in relevant target tissues.One PDE type 4 inhibitor, rolipram, has been shown to have antidepressant effects (Zhu et al 2001;Bobon et al 1988, Eckmann et al 1988. Rolipram was first demonstrated to have potent antidepressant activity in animal models (Zhu et al 2001;Wachtel and Schneider 1986).…”

Rolipram and Its Optical Isomers, Phosphodiesterase 4 Inhibitors, Attenuated the Scopolamine-Induced Impairments of Learning and Memory in Rats

“…It has been demonstrated to be effective against depressive disorders in clinics and in experimental animals (20)(21)(22) and has different effects on the monoaminergic system compared with those of the known monoaminergic agents. It has been suggested that rolipram has an accelerating effect on noradrenergic transmission by both an enhancement of noradrenergic turnover presynaptically (23) and an inhibition of cAMP degradation postsynaptically (24).…”

Design, Synthesis and Biological Evaluation of Novel Quinazoline-Based Anti-inflammatory Agents Acting as PDE4B Inhibitors

“…Unfortunately, its narrow therapeutic index, emesis and other adverse effects limited its use. [14][15][16][17][18] A breakthrough of PDE4 inhibitors as anti-inflammatory agents came up with second generation Roflumilast (3) Dexas ® by Merck Sharp & Dohme, a selective, long-acting inhibitor of the enzyme PDE4B. [19][20][21][22] Continuous efforts in this era lead to the discovery of Cilomilast (4) Ariflo ® , the most advanced PDE4 inhibitor developed by GSK.…”