Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs

Arzneimittelforschung. 1976;26(8):1551-6.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Analgesia
  • Analgesics, Opioid* / administration & dosage
  • Analgesics, Opioid* / toxicity
  • Anilides / administration & dosage
  • Anilides / pharmacology
  • Anilides / toxicity
  • Animals
  • Antiemetics
  • Apomorphine / antagonists & inhibitors
  • Dogs
  • Female
  • Fentanyl / pharmacology
  • Injections, Intravenous
  • Lethal Dose 50
  • Male
  • Meperidine / pharmacology
  • Mice
  • Mice, Inbred Strains
  • Morphine / pharmacology
  • Nalorphine
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Piperidines / toxicity
  • Pupil / drug effects
  • Rats
  • Rats, Inbred Strains

Substances

  • Analgesics, Opioid
  • Anilides
  • Antiemetics
  • Piperidines
  • Morphine
  • Meperidine
  • Apomorphine
  • Nalorphine
  • Fentanyl