Multiple mechanisms of action: the pharmacological profile of budipine

Eltze, Manfrid

doi:10.1007/978-3-7091-6360-3_4

Cited by 15 publications

(6 citation statements)

References 53 publications

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“…These studies have largely focused on the effects of these drugs on the dopaminergic system due to their clinical role in Parkinson's disease. Both have been shown to potentiate the activity of L ‐DOPA decarboxylase as well as inhibiting monoamine oxidase B (Eltze, 1999; Fisher & Starr, 2000) and to increase extracellular DA. Fisher & Starr (2000) have also reported regional effects of these drugs on the activity 5‐hydroxy‐tryptophan decarboxylase in the substantia nigra and striatum of rats.…”

Section: Discussionmentioning

confidence: 99%

Effects of amantadine and budipine on antidepressant drug‐evoked changes in extracellular 5‐HT in the frontal cortex of freely moving rats

Owen

Whitton

2005

British J Pharmacology

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1 Evidence has recently suggested that NMDA receptors may play a role in the aetiology and possible treatment of depression and that weak noncompetitive NMDA receptor antagonists such as amantadine can synergize with conventional antidepressants in a model of the illness. 2 To try to obtain a neurochemical rationale for these findings, we have studied the effects of acute and chronic administration of amantadine or the related drug budipine on cortical release of 5-hydroxytryptamine (5-HT) following the antidepressants reboxitine (REB), paroxetine (PAROX) and clomipramine (CLOM) in freely moving rats by using microdialysis. ) all failed to significantly alter extracellular 5-HT in the cortex. However, when either amantadine or budipine was administered 30 min prior to any of the three antidepressants, a significant rise in 5-HT was observed. 4 For chronic studies, the effects of the drugs were studied at 4, 7, 14 and 21 days. Amantadine and budipine did not significantly alter extracellular 5-HT at any time point. The three antidepressant drugs all elicited a gradual increase in 5-HT, which became significant after 14 days and tended to plateau thereafter. When either amantadine (20 mg kg À1 ) or budipine (5 mg kg À1 ) was coadministered with any of the three antidepressants, two differences were seen compared with the effects of the antidepressants alone. Firstly, the time required for significant increases in cortical 5-HT was reduced with elevated levels now being observed by 7 days. Secondly, the absolute magnitude of the increase in extracellular 5-HT was markedly greater in these rats from day 7 until the end of the experiment. 5 If, as is widely considered, an increase in extracellular 5-HT represents a critical step in the mechanism of action of antidepressants, these data suggest that combined treatment with clinically tolerated NMDA antagonists such as amantadine could reduce the delay in therapeutic onset of antidepressants as well as possibly enhance their efficacy.

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Section: Discussionmentioning

confidence: 99%

Effects of amantadine and budipine on antidepressant drug‐evoked changes in extracellular 5‐HT in the frontal cortex of freely moving rats

Owen

Whitton

2005

British J Pharmacology

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“…This is not necessarily a limitation of these drugs, especially when it is considered that the usefulness of TPM as an anticonvulsant possibly stems from its broad pharmacologic mechanisms of action. The pharmacologic profile of budipine has been well characterized (16,45). It has been shown to interact with the dopaminergic (46,47), cholinergic (17,48), serotonergic (49), and GABAergic systems (50).…”

Section: Discussionmentioning

confidence: 99%

“…NMDA-receptor antagonists exhibit limited clinical effectiveness on account of their psychotomimetic side effects. However, evidence suggests that low-affinity NMDA-receptor antagonists such as budipine and memantine may display beneficial effects in the early treatment of some clinical conditions such as Parkinson's disease (15,16) and epilepsy (17 channels; potentiation of γ -aminobutyric acid (GABA)-mediated inhibitory neurotransmission, and the activation of K + channels (18,19). The actions of TPM on GABA A receptors are not mediated through the benzodiazepine (BZD) or barbiturate sites.…”

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confidence: 99%

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

et al. 2004

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Summary:Purpose: To evaluate the antiepileptic and neuroprotective properties of topiramate (TPM) alone and with coadministration of the N-methyl-D-aspartate (NMDA)-receptor antagonist budipine in a rat model of refractory status epilepticus.Methods: Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer of the hippocampus under halothane anesthesia. Approximately 1 week after surgery, the perforant path of each animal was electrically stimulated for 2 h to induce self-sustaining status epilepticus. Successfully stimulated rats were given intraperitoneally vehicle (n = 6), TPM (20-320 mg/kg; n = 28), budipine (10 mg/kg; n = 5), or budipine (10 mg/kg) and TPM (80 mg/kg; n = 6) 10 min after the end of the stimulation and monitored behaviorally and electroencephalographically for a further 3 h.The animals were killed 14 days later, and histopathology was assessed.Results: Neither budipine alone nor TPM at any dose terminated status epilepticus. Despite this, TPM resulted in various degrees of neuroprotection at doses between 40 and 320 mg/kg. Coadministration of budipine with TPM terminated the status epilepticus in all rats. This combination also significantly improved the behavioral profile and prevented status-induced cell death compared with control.Conclusions: Budipine and TPM are an effective drug combination in stopping self-sustained status epilepticus, and TPM alone was neuroprotective, despite the continuation of seizure activity.

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“…The equivalent water-elimination intermediate, (6) is not chemically possible in sila-haloperidol as the silicon-carbon double bond would not be stable under physiological conditions. Hence, sila-haloperidol may show a more favorable side effect profile in vivo as compared to haloperidol.…”

Section: Sila-haloperidolmentioning

confidence: 99%

“…Its pharmacological profile has been reviewed [6] and aspects of its physicochemical properties have also been investigated. In the late 1980's Stasch [7] reported on the substitution of a carbon with a silicon atom within the core of 4,4-diphenyl budipine derivatives and the effect on the lipophilicity of the derivatives.…”

Section: Sila-budipinementioning

confidence: 99%

Silicon Switches of Marketed Drugs

Pk¹,

Ga²

2006

MRMC

105

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The application of organosilicon chemistry is a strategy to develop best in class drugs applied to targets that have been validated as tractable and drug-able. Silicon switches of known drugs have been synthesised and evaluated in biological assay systems then compared to their marketed all-carbon counterparts. Recent examples include the silicon switches of drugs haloperidol, fexofenadine, bexarotene and venlafaxine.

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Multiple mechanisms of action: the pharmacological profile of budipine

Cited by 15 publications

References 53 publications

Effects of amantadine and budipine on antidepressant drug‐evoked changes in extracellular 5‐HT in the frontal cortex of freely moving rats

Effects of amantadine and budipine on antidepressant drug‐evoked changes in extracellular 5‐HT in the frontal cortex of freely moving rats

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

Silicon Switches of Marketed Drugs

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