HS-599 is a didehydroderivative of buprenorphine that displays high affinity and good selectivity for it-opioid receptors. We studied its antinociceptive properties after s.c. injection in mice with the tail-flick and hot-plate tests. In the tail-flick test HS-599 (AD(50) = 0.2801 mumol/kg s.c.) behaved as a full agonist and was twice as potent as buprenorphine (AD(50) = 0.4569 mumol/kg s.c.) and 50 times more potent than morphine (AD(50) = 13.3012 mumol/kg s.c.). Whereas the mu-opioid receptor antagonists naloxone (1 - 10 mg/kg s.c.) and naltrexone (5-15 mg/k- s.c.) antagonized HS-599 induced analgesia, the delta-opioid receptor antagonist naltrindole (20 mg/kg s.c.) and the n-opioid receptor antagonist nor-binaltorphimine (20 mg/kg s.c.) did not. With the hot-plate test at 50degreesC, HS-599 (AD(50) = 0.0359 mumol/kg s.c.) was a full agonist about 130 times more potent than morphine (AD(50) = 4.8553 mumol/kg s.c.). With a high intensity nociceptive stimulus (55degreesC) HS-599 (AD(50)= 1.0382 mumol/kg s.c.) remained 7 times more potent than morphine (AD(50) = 7.0210 mumol/kg s.c.) but never exceeded the 55% of the maximum possible effect, behaving as a partial agonist able to antagonize morphine antinociception in a dose-dependent manner. HS-599 promises to be a potent and safe new analgesic, preferentially acting at spinal level.
Antinociceptive activity of a novel buprenorphine analogue / Lattanzi, Roberta; Negri, Lucia; Schmidhammer, H.; Giannini, Elisa. - In: LIFE SCIENCES. - ISSN 0024-3205. - STAMPA. - 70:(2002), pp. 2177-2185. [10.1016/S0024-3205(10)01553-3]
Antinociceptive activity of a novel buprenorphine analogue
LATTANZI, Roberta;NEGRI, Lucia;GIANNINI, Elisa
2002
Abstract
HS-599 is a didehydroderivative of buprenorphine that displays high affinity and good selectivity for it-opioid receptors. We studied its antinociceptive properties after s.c. injection in mice with the tail-flick and hot-plate tests. In the tail-flick test HS-599 (AD(50) = 0.2801 mumol/kg s.c.) behaved as a full agonist and was twice as potent as buprenorphine (AD(50) = 0.4569 mumol/kg s.c.) and 50 times more potent than morphine (AD(50) = 13.3012 mumol/kg s.c.). Whereas the mu-opioid receptor antagonists naloxone (1 - 10 mg/kg s.c.) and naltrexone (5-15 mg/k- s.c.) antagonized HS-599 induced analgesia, the delta-opioid receptor antagonist naltrindole (20 mg/kg s.c.) and the n-opioid receptor antagonist nor-binaltorphimine (20 mg/kg s.c.) did not. With the hot-plate test at 50degreesC, HS-599 (AD(50) = 0.0359 mumol/kg s.c.) was a full agonist about 130 times more potent than morphine (AD(50) = 4.8553 mumol/kg s.c.). With a high intensity nociceptive stimulus (55degreesC) HS-599 (AD(50)= 1.0382 mumol/kg s.c.) remained 7 times more potent than morphine (AD(50) = 7.0210 mumol/kg s.c.) but never exceeded the 55% of the maximum possible effect, behaving as a partial agonist able to antagonize morphine antinociception in a dose-dependent manner. HS-599 promises to be a potent and safe new analgesic, preferentially acting at spinal level.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.