Simple determination of K(A) or K(D) values makes it possible to calculate the standard free energy DeltaG degrees = -RTlnK(A) = RT lnK(D)(T= 298.15 K) of the binding equilibrium but not that of its two components as defined by the Gibbs equation DeltaG degrees = DeltaH degrees - TDeltaS degrees where DeltaH degrees and DeltaS degrees are the equilibrium standard enthalpy and entropy, respectively. Recently, it has been shown that the relative DeltaH degrees and DeltaS degrees magnitudes can often give a simple "in vitro" way for discriminating "the effect", that is the manner in which the drug interferes with the signal transduction pathways. This particular effect, called "thermodynamic discrimination", results from the fact that binding of antagonists may be enthalpy-driven and that of agonists entropy-driven, or vice-versa. In the past, the thermodynamic discrimination was reported for the beta-adrenergic G-protein-coupled receptor (GPCR) and confirmed later for adenosine A(1), A(2A) and A(3) receptors. Moreover, it has been found that the binding of all ligand-gated ion-channel receptors (LGICR) investigated was thermodynamically discriminated. In particular, affinity constants for typical neuronal nicotinic receptor ligands were obtained by both saturation and inhibition experiments with the radioligand [(3)H]-cytisine, a ganglionic nicotinic agonist. Thermodynamic parameters indicated that agonistic binding was both enthalpy- and entropy-driven, while antagonistic binding was totally entropy-driven. These results have shown that neuronal nicotinic receptor agonists and antagonists were thermodynamically discriminated. On these grounds, the thermodynamic behaviour makes it possible to discriminate drug pharmacological profiles in vivo through binding experiments in vitro.