Pharmacological Promiscuity and Its Clinical Interpretation

Most antipsychotic compounds are known to bind to many different receptors, especially those for serotonin, dopamine andhistamine [32,33]. Such pharmacological 

It can however be used in a standardized profiling panel calibrated against known promiscuous compounds. The THR classification given above is used in the Novartis in vitro safety pharmacology profiling panel where 50 targets have been tested. 

Promiscuity dropped to 5% in a subset of 132 most often prescribed and top selling drugs ( Top selling ). This contrasts with the 31% promiscuity found in the Novartis clinical candidates (CCs) which were discontinued. The most recent Novartis development candidates (DCs) on the other hand were very com parable to the best selling marketed drug set. 

It is important to point out that when a compound is pharmacologically promiscuous in a panel of 50 diverse targets, it is highly likely that the compound also hits several additional targets which are not included in the panel, thereby further increasing the liability risk. The reasons why certain compounds are more promiscuous than others and how promiscuity can be avoided is discussed in Chapter 13. 

If pharmacological promiscuity is strongly reduced and only very few activities remain, a risk assessment has to be performed based on the therapeutic index. 

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