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

Nishiyama, Mariko; Kuga, Tetsurō

doi:10.1254/jjp.50.167

Cited by 15 publications

(14 citation statements)

References 12 publications

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“…Since this area of the reticular formation is considered to be a part of the brain stem facilitatory areas proposed by Lindsley et al (7), it is likely that the FTA-induced genera lized tonic-clonic convulsion is a con sequence of excessively increased activity of the reticulospinal facilitatory pathways. This assumption is also supported by the previous observation that FTA failed to cause con vulsion after spinalization (4).…”

Section: Discussionsupporting

confidence: 80%

“…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: 82%

“…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). How ever, so far, there has been no direct evidence of FTA-induced abnormal activity of the brain stem, to which this severe convulsion might be attributable.…”

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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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 82%

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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“…Fumitremorgin C (FTC) was the first identified selective inhibitor of ABCG2, completely reversing mitoxantrone resistance in ABCG2 cells. This natural product was isolated from Aspergillus fumigatus , but turned out to be clinically useless owing to its neurotoxicity . Based on the indolyl diketopiperazine moiety, several structurally related analogues were developed, especially the less toxic and more potent inhibitor Ko143, the clinical use of which is limited by metabolic instability due to its Boc‐ester group .…”

Section: Introductionmentioning

confidence: 99%

Optimization of Acryloylphenylcarboxamides as Inhibitors of ABCG2 and Comparison with Acryloylphenylcarboxylates

et al. 2016

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ABCG2 belongs to the superfamily of ATP binding cassette (ABC) proteins and is associated with the limited success of anticancer chemotherapy, given its responsibility for the cross-resistance of tumor cells, known as multidrug resistance (MDR). Several classes of ABCG2 inhibitors were developed for increasing the efficacy of chemotherapy. A series of chalcones coupled to an additional aromatic residue was synthesized and investigated for their inhibition of ABC transporters. In our previous work we determined the preferred position of the linker on the A-ring to be ortho, and found several substitution patterns at the additional ring that improved potency. In this study we investigated whether a methoxy group that improved the inhibitory activity of chalcones would also be beneficial for the acryloylphenylcarboxamide scaffold. Indeed, this modification led to highly potent ABCG2 inhibitors. To support the hypothesis of a beneficial effect of the amide linker, six acryloylphenylcarboxylates were synthesized and investigated for their inhibitory activity. Replacement of the amide linker with an ester group resulted in decreased inhibition. Molecular modeling showed that the conformational preference of both series differs, thereby explaining the positive effect of the amide linker. Several compounds were characterized in detail by investigating their intrinsic cytotoxicity and capacity to reverse MDR in MTT assays and their effect on vanadate-sensitive ATPase activity.

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“…Abnormal activation of these cells by the mycotoxin could in turn lead to convulsive burst discharges in peripheral motor nerves. This may account for the typical epileptogenic effect of fumitremorgin A (Nishiyama and Kuga, 1989;Nishiyama and Kuga, 1990). A similar effect was exerted also by verruculogen (Bikson et al, 2002).…”

Section: Indole Alkaloidsmentioning

confidence: 77%

Chemistry and biological activity of azoprenylated secondary metabolites

2009

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

Cited by 15 publications

References 12 publications

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

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

Optimization of Acryloylphenylcarboxamides as Inhibitors of ABCG2 and Comparison with Acryloylphenylcarboxylates

Chemistry and biological activity of azoprenylated secondary metabolites

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