Dpmt. Of Pharmacology
Govt. Medical College ,Kottayam
Phosphodiesterases isolated from rat brains by
Uzunov and Weiss in 1972
The phosphodiesterase (PDE) story begins with
the work of Henry Hyde Salter in 1886. An
asthmatic he noted that when he drank a strong
cup of coffee on an empty stomach, his breathing
eased, an effect attributed to the bronchodilator
properties of caffeine.
Inhibits maturation of platelets from
Also inhibits PDE 3 & phospholipase A2
Headache, diarrhoea, fatigue, nausea, dizziness,
Less common side effects – MI, CHF,
Other PDE 2 Inhibitors
anti-viral, anti-tumour and anti-arrhythmic effects
BAY 60-7550 is an analog of EHNA.
dimethoxybenzyl)-purin-6- 5) and Oxindole .
No clinical use
Used as investigative tool in pharmacological research
Inamrinone, milrinone and Enoximone
↑ force of contraction, ↑HR
Use short-term treatment of cardiac failure.
Vasodilator & anti aggregatory
Use intermittent claudication.
Pimobendan - for veterinary use in the treatment of
heart failure in animals.
PDE 3 INHIBITORS
PDE 4 INHIBITORS
used to alleviate renal colic pain, hasten cervical
dilatation in labor
a neuroprotective and bronchodilator drug used in
asthma and stroke.
psoriasis and psoriatic arthritis
investigative tool in pharmacological research
1. Corpus cavernosum (highly selective)
2. Bladder neck
Tadalafil more potent & longer acting, slow
Headache, nasal congestion, flushing,
Disturbance in colour vision due to inhibition of
PDE 6 in retina.
Ability to potentiate NO use cautiously in
patients on nitrates
Vardanafil prolongs Q-T interval
Future trends in PDE 5 inhibitors
Female sexual arousal disorder
Inhibits PDE5 & 6.
Also inhibits cellular uptake of adenosine
Coronary vasodilator used in the treatment of angina
Post MI (to prevent coronary thrombosis)
Prosthetic valves (+Warfarin)
Post stroke (+Aspirin)
PDE7 selective inhibitors
Quinazoline type PDE7 inhibitor - potent anti-
inflammatory and neuroprotective agent.
PDE10 selective inhibitors
Papaverine, an opium alkaloid
PDE10A is almost exclusively expressed in
Use Erectile dysfunction (PIPE therapy)
PDE Inhibitors exerts its action by preventing the
degradation of second messenger molecules thereby
augmenting their effect in various tissues causing
smooth muscle relaxation,increased neuronal
plasticity,antiplatelet action etc.
Many more PDE Inhibitors are yet to come
Selective PDE inhibitors are being investigated in a
wide range of diseases including the use of PDE2
inhibitors in sepsis; PDE5 inhibitors to treat sexual
dysfunction in females, cardiovascular disease and
pulmonary hypertension; and PDE4 inhibitors to treat
asthma, COPD, allergic rhinitis, psoriasis, multiple
sclerosis, depression, Alzheimer's disease and