The pharmacology of betahistine in the context of the vestibular system

The problem of deciding, which, of several drug actions is the 'true' mechanism of action is an ancient and difficult one in pharmacology. Sometimes the problem is that each investigator may see his described action as through a tunnel, his vision not encompassing other possibilities. To help with the process of deciding the 'true' mechanism of action, the pharmacologist Philip Seeman has offered some guidelines. A few of his guidelines apply in the case of betahistine (BH). One is--does the drug have access to the proposed site of action? A second is--are the concentrations at which the drug acts at the candidate mechanism achievable in the patient? The three candidate sites of BH action are vascular, central nervous system and inner ear. There is obvious evidence that a vascular site as well as a vestibular end organs site are possible. There is also evidence that BH gains access to the central nervous system albeit achieving lower concentrations there than in plasma. Whether BH crosses the blood-labyrinthine barrier is not known. Then there is the guideline of similarity of clinically-achievable and experimental concentrations. Implicit in this guideline, without data to the contrary, is the assumption that the plasma concentration of a drug is roughly the concentration at the active site. This may or may not be true.