Psychomotor, respiratory and neuroendocrinological effects of nalbuphine and haloperidol, alone and in combination, in healthy subjects.
1. Actions and interactions on performance and respiration of single intramuscular doses of 0.15 mg kg-1 nalbuphine and oral haloperidol twice daily for 2 days were studied double-blind and cross-over in 12 healthy volunteers. 2. Objective measurements of performance (choice reaction, tracking, attention, flicker fusion, Maddox wing, digit symbol substitution) and respiratory function (minute volume, end-tidal carbon dioxide), and subjective assessments on visual analogue scales were done at baseline and 1 h, 2.5 h and 4 h after the injection of nalbuphine. Plasma concentrations of nalbuphine were estimated by radioreceptor ([3H]-dihydromorphine) assay, and those of prolactin and growth hormone by radioimmunoassay. 3. Nalbuphine affected digit substitution, reaction time, extraocular muscle balance and flicker recognition, and depressed respiration most clearly 1 and 2.5 h post injection. Motor skills were impaired only briefly. Haloperidol alone proved inert on performance but enhanced the decremental effects of nalbuphine on digit substitution and exophoria at 1 h. It did not interact with nalbuphine on the ventilatory function. 4. Plasma concentrations of nalbuphine expressed as morphine equivalents ranged from 5 to 52 ng ml-1, indicating considerable mu-opiate affinity. Treatment with haloperidol increased plasma prolactin moderately whilst nalbuphine raised it markedly 1 and 2.5 h post injection. Nalbuphine elevated plasma growth hormone at 1 h post injection only.
Saarialho-Kere
U
U
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
D000328:Adult; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009266:Nalbuphine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D011897:Random Allocation; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests
D009019:Morphinans; D006220:Haloperidol; D009266:Nalbuphine