[Interaction of tropoxin and its molecular fragments tropan and 3,4,5-trimethoxybenzoate with serotonin receptors of cortical neurons in the rat brain (a microionophoretic study)].
The effects of the antimigraine drug tropoxin and its main molecular fragments - tropan and 3,4,5-trimetoxybenzoate (TMB) - on the serotonin sensitivity of postsynaptic neuronal membrane in rat brain sensorimotor area has been studied using a microionophoretic (MIP) technique. All the three substances significantly reduce the excitatory neuronal response to serotonin, which is manifested by an increase in the rate of the spontaneous action potentials. With respect to the antiserotonin effect, the substances can be arranged in the following order: tropoxin > tropan > TMB. The sum of the effects of tropan and TMB (for both simultaneous and separate action upon the target cells) was significantly lower than the effect of tropoxin in all doses (MIP currents). It is concluded that a pronounced antiserotonin effect of tropoxin is produced only provided that the entire molecular configuration is retained. Tropan and TMB, being tropoxin metabolites, are probably capable of prolonging the antimigraine action upon the decay of tropoxin in the organism. A relationship between the structure and action of serotonin receptor blockers of the tropan series is discussed.
Kozhechkin
S N
SN
Kostochka
L M
LM
Bezhanian
S G
SG
Mirzoian
R S
RS
Seredin
S B
SB
D000818:Animals; D001372:Aza Compounds / Q000008:administration & dosage / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000378:metabolism*; D013329:Structure-Activity Relationship
C114333:3-(3,4,5-trimethoxybenzoyloximino)-8-methyl-8-azabicyclo(3,2,1)octane; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists