The acute effects of the enkephalin analogue BW 942C in humans

BW 942C hydrochloride is an enkephalin analogue that has exhibited a wide separation between antidiarrheal dosages and dosages inducing adverse effects in animals. This has likewise been the case in humans when administered orally. In this study, the safety and tolerance of single 0.5-mg doses of intravenous BW 942C compared with placebo were assessed in humans. Four healthy male volunteers received BW 942C, and two received placebo. The effects of BW 942C on serum growth hormone (GH), luteinizing hormone (LH), prolactin (PR), and follicle-stimulating hormone (FSH) were assessed in three of these volunteers. No significant changes were apparent in vital signs, in clinical chemistry, hematologic and urine studies following BW 942C administration. BW 942C did not appear to alter mood as assessed by two psychologic mood scales. Prolactin levels tended to increase in volunteers receiving BW 942C two hours postinfusion. Luteinizing hormone concentrations decreased slightly at two and six hours. No trends in FSH or GH could be identified. Pulmonary function testing did not reveal any significant changes in oximetry, spirometry, or plethysmography in any of the subjects. A marked decrease in CO2 responsiveness in two subjects may indicate that BW 942C has mild ventilatory depressant effects. Untoward effects experienced in volunteers receiving BW 942C included heaviness in the limbs, nasal stuffiness, mouth dryness, facial flushing, skin rash, and prickling sensations. These effects bear a striking similarity to those experienced after parenteral administration of other enkephalin analogues. Intravenous administration of BW 942C up to 0.5 mg appears safe from a laboratory, physiologic, and clinical perspective with unusual untoward effects that may preclude rational use of the drug by the parenteral route.