PMID- 2046456
OWN - NLM
STAT- MEDLINE
DCOM- 19910712
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 48
IP  - 23
DP  - 1991
TI  - Centrally-mediated antinociceptive action of RWJ-22757 (formerly McN-5195): 
      involvement of spinal descending inhibitory pathways (an hypothesis).
PG  - 2233-41
AB  - The present studies were an attempt to examine the mechanism of action of the 
      novel antinociceptive compound RWJ-22757, 
      (+/-)-trans-3-(2-bromophenyl)-octahydroindolizine (McN-5195). 
      Intracerebroventricular (i.c.v.) administration of RWJ-22757 produced 
      dose-related antinociception in the mouse tail-flick (48 degrees C) and rat 
      hot-plate (51 degrees C) tests (ED50 = 243.3 and 261.3 micrograms, respectively). 
      In contrast, intrathecal (i.t.) administration was without effect. The 
      antinociception produced by peripherally (i.p.) or centrally (i.c.v.) 
      administered RWJ-22757 was attenuated by i.t. administration of 2 micrograms 
      phentolamine, 5 micrograms yohimbine, or 10 micrograms methysergide. I.t. 
      administration of naloxone, at a dose (0.5 micrograms) that significantly 
      attenuated the antinociceptive effects of peripherally or centrally administered 
      morphine, had no effect on RWJ-22757-induced antinociception. We conclude from 
      these results, coupled with the overall pharmacological and neurochemical profile 
      of RWJ-22757, that the data are consistent with the hypothesis that RWJ-22757 
      produces antinociception predominantly at a site or sites located supraspinally 
      with little or no activity at the spinal level and that RWJ-22757 activates 
      adrenergic and serotonergic descending inhibitory pathways, increasing the tonic 
      activity of endogenous antinociceptive systems.
FAU - Vaught, J L
AU  - Vaught JL
AD  - Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Spring 
      House, PA 19477-0776.
FAU - Raffa, R B
AU  - Raffa RB
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Analgesics)
RN  - 0 (Indolizines)
RN  - 103729-18-6 (3-(2-bromophenyl)octahydroindolizine)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 36B82AMQ7N (Naloxone)
RN  - 76I7G6D29C (Morphine)
RN  - XZA9HY6Z98 (Methysergide)
RN  - Z468598HBV (Phentolamine)
SB  - IM
MH  - Analgesics/*pharmacology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Indolizines/*pharmacology
MH  - Injections, Intraventricular
MH  - Injections, Spinal
MH  - Male
MH  - Methysergide/pharmacology
MH  - Mice
MH  - Morphine/pharmacology
MH  - Naloxone/pharmacology
MH  - Phentolamine/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Spinal Cord/*drug effects
MH  - Yohimbine/pharmacology
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 0024-3205(91)90338-C [pii]
AID - 10.1016/0024-3205(91)90338-c [doi]
PST - ppublish
SO  - Life Sci. 1991;48(23):2233-41. doi: 10.1016/0024-3205(91)90338-c.