Background and Purpose: Allosteric sites on G Protein-Coupled Receptors have become increasingly popular drug targets as they can lead to the development of more selective compounds. An example is the D2 receptor, a validated drug target for numerous anti-psychotic drugs. In this study, we sought to gain a better understanding of the relationship between allosteric ligands and different orthosteric compounds. We investigated the UCB compound, a PAM-antagonist when treated with Dopamine, to see if it exhibits probe dependence and compared against other signalling pathways in relation to the allosteric site to gain insight into the improved design of a more selective D2R allosteric modulator. Experimental Approach: Dopamine, Quinpirole and Rotigotine were tested with/without the UCB compound. Forskolin-induced cAMP accumulation, Gi2 protein activation and β-arrestin2 protein recruitment real-time signalling pathways were assessed through transient transfection with the appropriate biosensors in HEK293 cells. Key Results: The UCB compound behaved as an allosteric antagonist with Quinpirole/Rotigotine in cAMP accumulation assays. However, in the β-arrestin2 protein recruitment assays, the UCB compound behaved as a PAM with all three agonists. Conclusions and Implications: The movement of the indole moiety of the UCB compound towards TM2 is important as it caused the switch from PAM-antagonism to antagonism in Forskolin-induced cAMP accumulation assays and a PAM in the β-arrestin2 protein recruitment assays. This provides insight to the functional groups required of a D2R allosteric modulator to interact with TM2. These findings may contribute towards the design of selective allosteric drugs targeting the D2R.