Phosphodiesterase-4 inhibitor


A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). 

PDE4 hydrolyzes cyclic adenosine monophosphate (cAMP) to inactive adenosine monophosphate (AMP). 

Inhibition of PDE4 blocks hydrolysis of cAMP, thereby increasing levels of cAMP within cells.

PDE4 hydrolyzes cyclic adenosine monophosphate to inactive adenosine monophosphate (AMP).

A member of the larger family of PDE inhibitors.

PDE-4B is a member of the type IV, cyclic AMP specific, cyclic nucleotide PDE family that plays a key role in signal transduction by regulating the cellular concentrations of cyclic nucleotides.


The PDE4 family of enzymes are the most prevalent PDE in immune cells.

The anti-inflammatory and immuno modulatory effects of oral selective PDE 4 are mediated by the ability of these inhibitors to increase   cAMP levels and are used for the treatment of certain inflammatory and auto immune diseases.

PDE4 inhibition prevents the hydrolysis of cAMP and suggests they are affective in inhibiting the proliferation and differentiation of fibroblasts as well as their ability to produce extracellular matrix in the presence of endogenous or endogenous cAMP trigger.

The PDE4 family of enzymes are the most prevalent PDE in immune cells. 

PDE4 enzymes are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system.

In the context of fibrosis,   cAMP antagonizes profibrotic signaling cascades.

The augmentation of cAMP levels represents a mechanism by which endogenous anti-fibrotic prostanoids prostaglandin E2 inhibits virtually all pertinent functions of normal fibroblasts.

Rolipram, is the prototypical PDE4 inhibitor.

PDE4 inhibitors possess procognitive and  long term memory-improving, wakefulness-promoting, neuroprotective, and anti-inflammatory effects. 

PDE4D inhibition, along with PDE4A inhibition is responsible for the antidepressant effects of PDE4 inhibitors.

Similarly PDE4B inhibition appears to be required for the antipsychotic effects of PDE4 inhibitors.

PDE4B polymorphisms and altered gene expression in the central nervous system have been associated with schizophrenia and bipolar disorders.

PDE4 regulates the signalling cascade in the frontal cortex, which may contribute to the antipsychotic and procognitive effects of PDE4 inhibitors.

PDE4 inhibition is also known to attenuate ethanol seeking and consumption in patients taking PDE4 oral medication for psoriasis.

PDE4 inhibitors have  potent emetic effects, which appear to be related to their inhibition of PDE4D which is expressed in the area postrema.

The clinical development of PDE4 inhibitors has been limited  by their potent emetic effects.

Adverse effects: Nausea, vomiting, and related general gastrointestinal side effects are the most commonly implicated.

Other possible side effects include respiratory and urinary tract infections.

Apremilast is approved for use as a treatment for psoriatic arthritis, and for the treatment of plaque psoriasis under the brand name Otezla.

Crisaborole drug for the topical treatment of psoriasis and atopic dermatitis.

Diazepam, a benzodiazepine anxiolytic, amnesic, hypnotic, sedative and muscle relaxant.

Ibudilast, a neuroprotective and bronchodilator drug.

Roflumilast, for the treatment of severe chronic obstructive pulmonary disease.

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