Chronic
diseases are due to deviations of fundamental physiological systems,
with different pathologies being characterised by similar malfunctioning
biological networks. The ensuing compensatory mechanisms may weaken the
body's dynamic ability to respond to further insults and reduce the
efficacy of conventional single target treatments. The multitarget,
systemic, and prohomeostatic actions emerging for plant cannabinoids
exemplify what might be needed for future medicines. Indeed, two
combined cannabis extracts were approved as a single medicine (Sativex®),
while pure cannabidiol, a multitarget cannabinoid, is emerging as a
treatment for paediatric drug-resistant epilepsy. Using emerging
cannabinoid medicines as an example, we revisit the concept of
polypharmacology and describe a new empirical model, the ‘therapeutic
handshake’, to predict efficacy/safety of compound combinations of
either natural or synthetic origin.
Trends
Some
successful ‘selective’ single target drugs were shown to act via
multiple mechanisms or ‘repositioned’ for the treatment of other
conditions because of their ability to interact with ‘off-targets’.
The
use of polypharmacy is not uncommon in clinical practice and represents
a way of addressing the multifactorial aetiology of disorders and their
ensuing complications and comorbidities.
Many tools
are available to accelerate discovery of single target drugs but new
models to predict the efficacy/safety of multitarget drugs and their
combinations are required.
A model is proposed here
to describe the spatiotemporal fit between target activation/repression
required in disorders and multitarget treatments.
‘Polypharmacological handprints’ are matched to ‘aetiopathological handprints’ establishing a ‘therapeutic handshake’.
Copyright © 2015 Elsevier Ltd. All rights reserved.
