Norepinephrine (NE) is a vasoconstricting neurotransmitter released from the sympathetic nerves that innervate the smooth muscle cells of arteries and veins. It is an important regulator of vascular tone. The molecule is electroactive and can be measured locally at the blood vessel surface using voltammetric or amperometric methods with both carbon fiber or boron-doped diamond microelectrodes. Several neuropharmacological agents are routinely employed in the study of noradrenergic neuroeffector transmission. With electrochemical methods, it is important to know (i) if a particular drug is electroactive at the potentials used to detect NE and or (ii) if exposure of the microelectrode to the drug causes any attenuation of the NE oxidation current because of drug adsorption and or fouling. We report herein on a cyclic voltammetric investigation of the electrochemical activity of several drugs commonly used to study sympathetic neuroeffector transmission, and how exposure to the drugs affects the electrode response sensitivity for NE. The performance of carbon fiber and diamond microelectrodes was compared. Results revealed that cocaine, idazoxan and PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate) are electrochemically inactive at both microelectrodes at the potentials used to detect NE, and drug exposure has little effect on the NE oxidation current. On the other hand, exposure to capsaicin, prazosin, yohimbine and UK 14,304 produced varying degrees of NE oxidation current attenuation at both microelectrode types. Furthermore, detection of NE in the presence of prazosin or capsaicin is complicated by the fact that both drugs are oxidized near the potentials used for NE monitoring. When yohimbine and UK 14,304 are present, NE can be detected but the oxidation current is reduced. The results demonstrate that the effect of any drug on the electrode response sensitivity and stability should be ascertained before making in vitro or in vivo electrochemical measurements using carbon fiber or diamond microelectrodes. (C) 2009 Published by Elsevier B.V.