Disease relevance of Budipine

• Budipine provides additional benefit in patients with Parkinson disease receiving a stable optimum dopaminergic drug regimen [1].
• Synergism between topiramate and budipine in refractory status epilepticus in the rat [2].
• Budipine reduced MPP+ toxicity in the nigrostriatal system of mice [3].
• Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine [4].
• Prophylactic treatment of cluster headache with budipine [5].

High impact information on Budipine

• Dopamine release was blocked by the centrally acting AADC inhibitor NSD 1015, but facilitated by the central AADC activator budipine [6].
• The NMDA receptor antagonistic effects of budipine were assessed using concentration- and patch-clamp techniques on cultured striatal, hippocampal, cortical and superior colliculus neurones [7].
• Budipine is a low affinity, N-methyl-D-aspartate receptor antagonist: patch clamp studies in cultured striatal, hippocampal, cortical and superior colliculus neurones [7].
• Budipine exhibited concentration-dependent open channel blocking kinetics (kappa(on) = 0.71 x 10(4) M(-1) s(-1)) whereas the fast offset rate was concentration-independent (kappa(off) = 0.63 s(-1)) [7].
• Whereas both drugs (1-10 microM) strongly increased spontaneous [3H]outflow in caudate nucleus slices preincubated with [3H]DA, budipine inhibited but biperiden facilitated the evoked DA release [8].

Chemical compound and disease context of Budipine

• To study whether budipine has dopaminergic activity in vivo, we used the 6-hydroxydopamine rotational model of Parkinson's disease [9].
• However, if the rats were pretreated with budipine, no MPTP-induced reduction in the dopamine and serotonin levels in the caudate nucleus was observed although one month recovery and observation time had elapsed between the last budipine injection and decapitation [10].

Biological context of Budipine

• Therefore, these two aromatic residues in the channel pore are likely to form a main part of the binding site for budipine.In summary, this is the first study that provides a molecular basis for the budipine-associated aLQTS observed in clinical practice [4].
• In receptor-binding assays, budipine inhibited thienylcyclohexylpiperidyl-3,4-[3H](n) ([I3H]TCP) (2.5 nM)-binding with an IC50 of 36 microM and [3H]3-quinuclidinol benzilate-binding with an IC50 of 1.1 microM [9].
• The area under the concentration vs time curve (AUC) and the maximum serum concentration (Cmax) showed a linear increase in line with ascending doses of orally given budipine [11].
• Dose linearity and steady state pharmacokinetics of the new antiparkinson agent budipine after oral administration [11].
• 10(-7), 10(-8), 10(-9) mol/l of budipine significantly reduced release of TNF-alpha and Il-6 in PBMC and decreased apoptotic cell death after 50 hours and 74 hours in the SH-SY 5Y cells [12].

Anatomical context of Budipine

• Effects of the antiparkinsonian drug budipine on neurotransmitter release in central nervous system tissue in vitro [8].
• The present study examined the effects of the antiparkinsonian drug budipine on dopamine synthesis and release from L-DOPA in the substantia nigra of reserpine-treated rats [13].
• Microdialysis study of the effects of the antiparkinsonian drug budipine on L-DOPA-induced release of dopamine and 5-hydroxytryptamine by rat substantia nigra and corpus striatum [14].
• In Xenopus oocytes, HERG potassium channels were blocked by budipine with an IC(50) of 10.2 microM [4].
• This study confirms the important role P-gp plays at the blood-brain barrier and shows that budipine is a substrate of P-gp [15].

Associations of Budipine with other chemical compounds

• The evoked release of [3H]ACh in rabbit caudate nucleus slices preincubated with [3H] choline was almost unaffected by budipine but enhanced by biperiden in the absence of further drugs [8].
• The antiparkinsonian drug budipine binds to NMDA and sigma receptors in postmortem human brain tissue [16].
• To advance a neurochemical rational for these findings, we have studied the effects of administration of amantadine and budipine with the antidepressants reboxetine (REB), paroxetine (PAROX) and clomipramine (CLOM) on extracellular DA in rats using microdialysis [17].
• During the course of the disease dopamine agonists, amantadine, budipine, COMT inhibitors and selegiline will be used [18].
• Prodipine and budipine inhibit the uptake of 14C-5-HT by human blood platelets in a dose-dependent manner [19].

Gene context of Budipine

• In addition, COMT inhibitors, budipine, amantadine and selegiline may be used [20].
• We have estimated the affinity of the antiparkinsonian drug budipine to the PCP binding site of the NMDA receptor and to sigma 1 binding sites in membranes from postmortem human brain frontal cortex [16].
• A MAO B-inhibitory component of budipine, as shown in receptor binding studies previously, could contribute to this effect [21].

Analytical, diagnostic and therapeutic context of Budipine

• To determine the impact of impaired hydromorphone formation on the behavioral effects of the parent compound, hydrocodone-induced analgesia and hyperactivity, hydrocodone discrimination and self-administration were examined in male Wistar rats, with or without pretreatment with CYP2D1 inhibitors (quinine and budipine) [22].
• In clinical trials budipine reduced tremor, akinesia and rigidity [3].
• Budipine is a potent non-dopaminergic antiparkinsonian drug with pharmacological effects that are not comparable to those of conventional drugs applied in Parkinsonian pharmacotherapy [23].
• To investigate whether the uptake of the anti-Parkinson drug budipine into the brain is mediated by P-glycoprotein, abcb1ab(-/-) double knock-out mice and wild-type control mice received budipine continuously over 11 days via implanted osmotic infusion pumps at the rate of 30ug over 24h [15].
• Effects of the antiparkinson drug budipine on EEG activity in unrestrained rats [24].

References