Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice.
The putative serotonin (5-HT) receptor antagonist metitepin (0.5 mg/kg, intraperitoneally) produced hypoalgesia in the increasing temperature hot-plate test and hyperalgesia in the tail-flick test in mice. The effects of metitepin were not altered after depletion of 5-HT by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms free base, intracerebroventricularly) or the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA, 400 mg/kg for 10 consecutive days). After chronic administration (2 or 5 mg/kg for 18 consecutive days) tolerance to the effect of metitepin (0.5 mg/kg) and cross-tolerance to the antinociceptive effect of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg) was found in the hot-plate test but not in the tail-flick test. It is suggested that metitepin may block descending 5-HT transmission while more complex mechanisms of action are involved at supraspinal level. One possibility is that metitepin exhibits partial agonist properties or, alternatively, that the drug may block 5-HT subsystems which tonically enhance nociception.
Eide
P K
PK
Department of Physiology, University of Bergen, Norway.
Hole
K
K
Berge
O G
OG
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D003988:Dibenzothiepins / Q000494:pharmacology*; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology*; D008297:Male; D008719:Methiothepin / Q000494:pharmacology*; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D011985:Receptors, Serotonin / Q000187:drug effects*
D003988:Dibenzothiepins; D004102:Dihydroxytryptamines; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D008719:Methiothepin; D010134:Fenclonine