Pre-ejection period (PEP) and T-wave amplitude (TWA) have been used to assess sympathetic nervous system (SNS) activity. Here we report two single-blinded, placebo-controlled intravenous (IV) drug application studies in which we pharmacologically modified SNS activity with epinephrine (study 1) as well as dexmedetomidine (alpha2-agonist) and yohimbine (alpha2-antagonist) (study 2). Restricted heart rate (HR) intervals were analyzed to avoid confounding effects of HR changes. Study 1 served to replicate previous findings and to validate our approach, whereas study 2 aimed to investigate how modulation of central SNS activity affects PEP and TWA. Forty healthy volunteers (58% females) participated in study 1 (between-subject design). Twelve healthy men participated in study 2 (within-subject design). TWA and PEP were derived from ECG and impedance cardiography, respectively. Epinephrine shortened PEP and induced statistically significant biphasic TWA changes. However, although the two alpha2-drugs significantly affected PEP as expected, no effects on TWA could be detected. PEP is better suited to reflect SNS activity changes than TWA.