2. HISTORY
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.
23. ANAGRALIDE
Inhibits maturation of platelets from
megakaryocytes
Also inhibits PDE 3 & phospholipase A2
USES
Essential thrombocytosis
ADR
Headache, diarrhoea, fatigue, nausea, dizziness,
hairloss.
Less common side effects – MI, CHF,
cardiomyopathy
24. Other PDE 2 Inhibitors
EHNA-Erythro-9-(2-hydroxy-3-nonyl)adenine
anti-viral, anti-tumour and anti-arrhythmic effects
BAY 60-7550 is an analog of EHNA.
PDP (9-(6-Phenyl-2-oxohex-3-yl)-2-(3,4-
dimethoxybenzyl)-purin-6- 5) and Oxindole .
No clinical use
Used as investigative tool in pharmacological research
25. Inamrinone, milrinone and Enoximone
(inodilator)
Cardiac stimulantion
↑ force of contraction, ↑HR
Vasodilatation
Use short-term treatment of cardiac failure.
Cilostazol
Vasodilator & anti aggregatory
Use intermittent claudication.
Pimobendan - for veterinary use in the treatment of
heart failure in animals.
PDE 3 INHIBITORS
26. PDE 4 INHIBITORS
Drotaverine
used to alleviate renal colic pain, hasten cervical
dilatation in labor
Roflumilast,Cilomilast
COPD
Ibudilast
a neuroprotective and bronchodilator drug used in
asthma and stroke.
Apremilast
psoriasis and psoriatic arthritis
Rolipram, Piclamilast
investigative tool in pharmacological research
29. ADRs
Headache, nasal congestion, flushing,
hypotension
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
31. Future trends in PDE 5 inhibitors
Premature ejaculation
Female sexual arousal disorder
Raynauds phenomenon
Stroke
32. DIPYRIDAMOLE
MOA
Inhibits PDE5 & 6.
Also inhibits cellular uptake of adenosine
Actions
Coronary vasodilator used in the treatment of angina
Antiplatelet action
Uses
Post MI (to prevent coronary thrombosis)
Prosthetic valves (+Warfarin)
Post stroke (+Aspirin)
ADR
Coronary steal
33. 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
the striatum
Use Erectile dysfunction (PIPE therapy)
34. Summary
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
schizophrenia.