The present article investigates the interactions of a resorcin[4]arene receptor with planar bilayer lipid membranes (BLMs) that can be used for the electrochemical detection of dopamine and ephedrine. BLMs were composed of egg phosphatidylcholine and 35% (w/w) dipalmitoyl phosphatidic acid in which the receptor was incorporated. These BLMs modified with the resorcin[4]arene receptor can be used as one-shot sensors for the direct electrochemical sensing of these energizing-stimulating substances. The interactions of these compounds with the lipid membranes were found to be electrochemically transduced in the form of a transient current signal with a duration of seconds, which reproducibly appeared within 8 and 20 s after exposure of the membranes to dopamine and ephedrine, respectively. The response time for BLMs without the receptor for dopamine was about 3 min, whereas no signals were obtained for ephedrine in the absence of the receptor. The mechanism of signal generation was investigated by differential scanning calorimetric studies. These studies revealed that the adsorption of the receptor is through the hydrophobic tails of the receptor, whereas hydrophilic groups of the receptor were directed towards the electrolyte solution enhancing the ion transport through the lipid membranes. The magnitude of the transient current signal was related to the concentration of the stimulating agent in bulk solution in the micromolar range. No interferences from ascorbic acid were noticed because of the use of the negatively charged lipids in membranes. The present technique can be used as one-shot sensor for the detection of these pharmaceutical substances and future research is targeted to the determination of these chemicals in human biofluids such as urine of athletes.