Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs.
Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, is a chemically novel, highly potent and extremely safe intravenous morphine-like agent in laboratory animals. In mice R 30 730 i.v. is 2304 times more potent than morphine (hot plate ED50's: 0.0028 and 6.45 mg/kg, respectively). The i.v. safety margin of R 30 730 in mice is 1 : 6 679 (LD50 = 18.7 mg/kg). Under the same experimental conditions the safety margin of pethidine is 1 : 7.97, of morphine 1 : 34.9 and of fentanyl 1 : 454. In rats R 30 730 i.v. is 4521 times more potent than morphine (tail withdrawal test ED50's: 0.00071 and 3.21 mg/kg, respectively). The i.v. safety margin of R 30 730 in rats is 1 : 25 211 (LD50 : 17.9 mg/kg). Under the latter experimental conditions the safety margin of pethidine is 1 : 4.80, of morphine 1 : 69.5 and of fentanyl 1 : 277. In dogs R 30 730 i.v. is 2429 times more potent than morphine (apomorphine antagonism test ED50's: 0.00028 and 0.68 mg/kg, respectively). The i.v. safety margin in dogs is approximately 1 : 50 000, the LD50 being +/- 14.0 mg/kg. All morphine-like effects of R 30 730 are immediately antagonized by nalorphine. These pharmacological findings are relevant in connection to the increasing interest for use of morphinomimetics in anesthesia.
D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000633:toxicity; D000813:Anilides / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000932:Antiemetics; D001058:Apomorphine / Q000037:antagonists & inhibitors; D004285:Dogs; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009269:Nalorphine; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011680:Pupil / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000701:Analgesics, Opioid; D000813:Anilides; D000932:Antiemetics; D010880:Piperidines; D009020:Morphine; D008614:Meperidine; D001058:Apomorphine; D009269:Nalorphine; D005283:Fentanyl