We wished to determine if drugs with negative inotropic properties would exacerbate the transient myocardial depression associated with intravenous (i.v.) cocaine administration. The influence of propranolol, nifedipine, or verapamil pretreatment on the myocardial depressant effect of cocaine was examined in 13 chronically instrumented, conscious dogs. Cocaine alone (4 mg/kg i.v.) caused significant increases in heart rate (HR), mean arterial pressure (MAP), and rate-pressure product (RPP), effects consistent with sympathetic stimulation. Regional ejection fraction (EF) (determined by two-dimensional echocardiography), however, decreased from 56 +/- 5% (mean +/- SE) at baseline to 34 +/- 6% at 1 min and to 41 +/- 5% at 2 min after cocaine administration but recovered to 49 +/- 4% at 10 min. Pretreatment with propranolol (0.5 mg/kg i.v.) blunted the rate-pressure response to cocaine by 28%. Regional EF decreased from 53 +/- 5% at baseline to 26 +/- 3% (p < 0.01 as compared with cocaine alone) at 2 min after cocaine and was still reduced at 33 +/- 3% (p < 0.001 as compared with cocaine alone) at 10 min. Pretreatment with verapamil (10 mg i.v. 10 min before cocaine) blunted the rate-pressure response very little, but regional left ventricular (LV) EF decreased less, from 58 +/- 3% to only 46 +/- 5% at 2 min, and was almost normal at 10 min (57 +/- 5%). Nifedipine [90 mg sustained-release orally (p.o.) administered 5 h earlier] also reduced the myocardial depressant effect of cocaine at 2 min [regional EF decreased from 50 +/- 2% at baseline to 38 +/- 4% (cocaine alone), 56 +/- 3 to 49 +/- 4% (nifedipine and cocaine), p < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)