The effects on resting ventilation of intravenous infusions of morphine or sameridine, a novel molecule with both local anesthetic and opioid properties.
Sameridine has both local anesthetic and partial mu-opioid receptor agonistic properties. The aim of this single-blinded, randomized, three-way cross-over study of 12 subjects was to investigate the effects on resting ventilation of two doses of sameridine: 0.15 mg/kg (S-Small) and 0.73 mg/kg (S-Large) compared with 0.10 mg/kg morphine. Each drug was infused IV over 20 min. Ventilation was measured by pneumotachography and in-line capnography, and sedation was rated by the subjects using a visual analog scale (VAS). Plasma was collected and analyzed for sameridine and morphine. At the end of drug infusion, minute ventilation (VE) and tidal volume (VT) were reduced in the S-Large group, and VE was reduced in the morphine group. End-tidal CO2 increased in both groups (P < 0.05), but respiratory rates remained unchanged. In the S-Small group, no ventilatory changes were recorded. In the S-Large group, the median sedation score was 6.8 cm with corresponding values in the morphine and S-Small groups of 3.3 and 2.5 cm, respectively. There was a relationship between the plasma concentration of sameridine and the depression of ventilation. We conclude that sameridine influences resting ventilation and that this effect is directly related to plasma concentrations of sameridine. From a ventilatory aspect, a clinical dose of sameridine with both local anesthetic and opioid properties seems safe.


CONCLUSIONS
Sameridine, a molecule with both local anesthetic and analgesic properties, impaired resting ventilation after a large IV dose (0.73 mg/kg), more so than 0.10 mg/kg IV morphine. A clinical dose of sameridine (0.15 mg/kg) did not have any effects on ventilation.
Osterlund
A
A
Department of Anaesthesiology and Intensive Care, Karolinska Hospital and Institute, Stockholm, Sweden.
Arlander
E
E
Eriksson
L I
LI
Lindahl
S G
SG
D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012146:Rest; D016037:Single-Blind Method
D000700:Analgesics; D000701:Analgesics, Opioid; D010880:Piperidines; D002245:Carbon Dioxide; D009020:Morphine; C113809:sameridine