Pharmacological Effects of the Tremorgenic Mycotoxin Fumitremorgin A

Nishiyama, Mariko; Kuga, Tetsurō

doi:10.1254/jjp.40.481

Cited by 14 publications

(13 citation statements)

References 19 publications

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“…When injected intravenously in experimental animals, FTA causes tremor and generalized tonic-clonic convulsion (2,3). The autonomic nervous system is also severely affected by this toxin (4), and all these effects may result from abnormal ex citation of the central nervous system (CNS).…”

mentioning

confidence: 99%

Central effects of the neurotropic mycotoxin fumitremorgin A in the rabbit. () Effects on the spinal cord.

Nishiyama

Kuga

1989

Jpn.J.Pharmacol

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Abstract-Effects of a potent neurotropic mycotoxin, fumitremorgin A (FTA), on the spinal cord were studied, using rabbits lightly anesthetized with urethane and chloralose.Spontaneous discharges of L7 spinal ventral roots and common peroneal nerves were increased after intravenous injection of 100-200 ug/kg of FTA. Their abnormal discharge pattern represented the convulsive effect of FTA. Spinal monosynaptic reflexes became irregular in amplitude, with a slight predominance of smaller reflexes.Polysynaptic reflexes were inhibited in many cases. These FTA-induced changes in ventral root discharges and spinal reflexes were abolished by spinal transection at a segment of the upper level. These results suggest that FTA may have no direct facilitatory action on spinal motoneurons and that its remarkable motor effect has its origin in the supraspinal central nervous system.

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confidence: 99%

Central effects of the neurotropic mycotoxin fumitremorgin A in the rabbit. () Effects on the spinal cord.

Nishiyama

Kuga

1989

Jpn.J.Pharmacol

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“…In previous studies, the main site of con vulsant action of FTA has been suggested to be in some restricted areas in the brain stem, from the mesencephalon to the medulla oblongata (3,4). In the present study, the role of the brain stem in the convulsant effect of FTA was investigated in anesthetized rabbits.…”

Section: Discussionmentioning

confidence: 83%

“…Only a few indirect findings are available at present. Our previous study has shown that the FTA induced EEG arousal response is quite dif ferent from the typical seizure pattern caused by pentylenetetrazol (3). Therefore the me chanism of action of FTA may be different from that of pentylenetetrazol, although this drug is assumed to increase neuronal ex citability through its direct action on the cell membrane (8), and the most important site of its action is also considered to be in the me sencephalon (9).…”

Section: Discussionmentioning

confidence: 99%

“…Curiously, however, this convulsion is never accompanied by an ap parent electroencephalographic seizure pat tern (3). The main site of the convulsant ac tion of FTA has been suggested to be in restricted areas in the brain stem (3,4).…”

Section: Fumitremorginmentioning

confidence: 99%

“…All ex periments were carried out under anesthesia with urethane and a-chloralose (400 mg/kg and 40 mg/kg, i.p., respectively), because it is known that tonic-clonic convulsions can take place under this anesthetic condition if a large dose (100-200 ,ag/kg, i.v.) of FTA is administered (3). In order to avoid the violent body movement caused by FTA, the animals were immobilized by pancuronium bromide (0.1 mg/kg, i.v., initially and repeated as needed) under artificial ventilation.…”

Section: Fumitremorginmentioning

confidence: 99%

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Central effects of the neurotropic mycotoxin fumitremorgin A in the rabbit. (II). Effects on the brain stem.

Nishiyama

Kuga

1990

Jpn.J.Pharmacol

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Abstract-In order to determine the main site of the convulsant action of the neuro tropic mycotoxin fumitremorgin A, the role of the brain stem reticular formation was studied.In rabbits lightly anesthetized with urethane and chloralose, electrical stimulation of the reticular formation elicited burst discharges in the common peroneal nerve and in the tibial nerve. This facilitatory effect of electrical stimu lation was markedly potentiated by intravenous administration of a small dose of FTA, before onset of actual convulsion.Under the influence of FTA, a remarkable increase in the spontaneous electrical activity of the midbrain reticular formation was observed.The firing pattern of some neurons in the reticular formation cor responded very well with abnormal burst discharges in the common peroneal nerve. These effects of FTA were inhibited by chlorpromazine (0.1-1.0 mg/kg, i.v.), diazepam (0.1-1.0 mg/kg, i.v.), mephenesin (5-10 mg/kg, i.v.) and pentobarbital (5-15 mg/kg, i.v.). It was concluded that FTA might activate some neurons in the midbrain reticular formation and that convulsive burst discharges in peripheral motor nerves resulted from abnormal activation of these neurons, although the role of the medullary reticular formation could not be excluded.

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