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talipexole (talipexole / Domin / alefexole)

✓ Approved

Boehringer Ingelheim International GmbH · DRD2 · 小分子

什么是 talipexole？

talipexole 是一种小分子，由Boehringer Ingelheim International GmbH研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名talipexole, Domin, alefexole
公司Boehringer Ingelheim International GmbH
药物类别小分子
分子靶点DRD2, HTR3A
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Boehringer Ingelheim International GmbH

作用机制

分子靶点

talipexole 作用于 2 个分子靶点：

DRD2dopamine receptor D2 (D2DR, D2R)
HTR3A5-hydroxytryptamine receptor 3A (5HT3R, HTR3)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

talipexole 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Nervous system disordersParkinson's disease✓ Approved

相关研究文献

PubMedNeuroreport2015-11-13

Duration of drug action of dopamine D2 agonists in mice with 6-hydroxydopamine-induced lesions.

Tsuchioka Akihiro A, Oana Fumiki F, Suzuki Takayuki T, Yamauchi Yuji Y et al.

Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson's disease model, the effects of dopamine D2 agonists in mice with 6-OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA-induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long-lived anti-Parkinson effects in rats and humans. In contrast, pramipexole and ropinirole had notably short durations of drug action. We demonstrated that mice with 6-OHDA-induced lesions accompanied with significant lesions in the striatum may be reasonable models to predict the action duration of anti-Parkinson drug candidates in humans.

PMID 26559726
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PubMedNihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology2014-12-30

[The therapeutic plasma concentrations of antiparkinson dopamine agonists and their in vitro pharmacology at dopamine receptors].

Tadori Yoshihiro Y, Kobayashi Hiroyuki H

This review discusses the relationship between therapeutic plasma concentrations of antiparkinson dopamine agonists (rotigotine, pergolide, cabergoline, apomorphine, bromocriptine, ropinirole, pramipexole, and talipexole) and their in vitro pharmacology at dopamine D1, D2 and D3 receptors. A significant correlation was found between therapeutic plasma concentrations of these dopamine agonists and their agonist potencies (EC50) at D2 receptors, although no such correlation existed at D1 or D3 receptors, suggesting that D2 receptors could be the primary and common target for the antiparkinson action of all dopamine agonists. However, D1 receptor stimulation is also important for maintaining swallowing reflex, bladder function and cognition. In particular, continuous D1 and D2 receptor stimulation may be reduced to low levels among Parkinson's disease patients. Our findings revealed therapeutic plasma concentrations of rotigotine were similar to its agonist potencies at both D1 and D2 receptors. Thus, rotigotine may be beneficial for the treatment of Parkinson's disease patients in that this dopamine agonist has the potential of continuous stimulation of both D1 and D2 receptors in the clinical setting.

PMID 25536763
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PubMedHuman fertility (Cambridge, England)2013-09-21

Do dopamine agonists prevent or reduce the severity of ovarian hyperstimulation syndrome in women undergoing assisted reproduction? A systematic review and meta-analysis.

Baumgarten Miriam M, Polanski Lukasz L, Campbell Bruce B, Raine-Fenning Nick N

Controlled ovarian stimulation is an integral part of assisted reproduction treatment. This can result in ovarian hyperstimulation syndrome (OHSS), which is associated with significant morbidity and potentially mortality. Recent approaches to ovarian stimulation have led to a reduction in the prevalence of OHSS but it still occurs. Dopamine agonists (DAs) have been used with some success during the ovarian stimulation phase when there are early signs of OHSS but there is no consensus on when to start and stop treatment or on the dose and specific agonist to use. EMBRASE, MEDLINE and Cochrane were searched using the following terms: ovarian hyperstimulation syndrome, controlled ovarian hyperstimulation, DAs, cabergoline, quinagolide, bromocriptide, pergolide, talipexole, ropinirole and pranipexole. The search yielded 20 publications. In total 1646 woman were included and 914 received a DA. In the treated group 86 (9.41%) developed OHSS, compared with 157 (21.45%) in the non-treated group. Nine studies were suitable for meta-analysis. This showed a benefit to the use of DAs (RR 0.51 [0.33, 0.78], Chi² = 16.07). The use of DAs appears to be effective for the prevention of OHSS. DAs are useful but less effective for the treatment of OHSS. No conclusions can be made regarding the most effective drug, the optimal dose or the most appropriate drug regimen.

PMID 24047196
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PubMedPathobiology : journal of immunopathology, molecular and cellular biology2013-08-31

Drug-induced hypothermia as beneficial treatment before and after cerebral ischemia.

Johansen Flemming F FF, Hasseldam Henrik H, Rasmussen Rune S RS, Bisgaard Anne Sofie AS et al.

Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke. Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced either immediately or with 3 h delay. Rats survived ischemia for 2, 7 or 90 days. Infarct volumes were quantified by stereology. Additional experiments of methodological relevance were included in the study. Talipexole induced mild hypothermia (35.1±1.1 to 36.0±0.5°C) for <20 h. Hypothermic pre- and postconditioning reduced infarct sizes by more than 60% as monitored during the first 90 days after experimental stroke (p<0.05). Talipexole is registered for use as a dopamine substitute in humans with Parkinson's disease. Although dosages cannot be directly translated to patients, our study exemplifies in an animal model that drug-induced hypothermia in a clinical setting might reduce cerebral ischemic damage before neuro- and cardiac surgical procedures and after stroke.

PMID 23989388
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PubMedEuropean journal of pharmacology2011-06-11

Functional potencies of dopamine agonists and antagonists at human dopamine D₂ and D₃ receptors.

Tadori Yoshihiro Y, Forbes Robert A RA, McQuade Robert D RD, Kikuchi Tetsuro T

We measured the functional agonist potencies of dopamine agonists including antiparkinson drugs, and functional antagonist potencies of antipsychotics at human dopamine D(2) and D(3) receptors. In vitro pharmacological assessment included inhibition of forskolin-stimulated cAMP accumulation and the reversal of dopamine-induced inhibition in clonal Chinese hamster ovary cells expressing low and high densities of human dopamine D(2L) and D(2S) receptors (hD(2L)-Low, hD(2L)-High, hD(2S)-Low and hD(2S)-High, respectively) and human dopamine D(3) Ser-9 and D(3) Gly-9 receptors (hD(3)-Ser-9 and hD(3)-Gly-9, respectively). Cabergoline, bromocriptine, pergolide, (±)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), talipexole, pramipexole, R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-olhydrochloride (PD128907) and ropinirole behaved as dopamine D(2) and D(3) receptor full agonists and showed higher potencies in hD(2L)-High and hD(2S)-High compared to hD(2L)-Low and hD(2S)-Low. In hD(3)-Ser-9 and hD(3)-Gly-9 compared to hD(2L)-Low and hD(2S)-Low, dopamine, ropinirole, PD128907, and pramipexole potencies were clearly higher; talipexole and 7-OH-DPAT showed slightly higher potencies; pergolide showed slightly lower potency; and, cabergoline and bromocriptine potencies were lower. Aripiprazole acted as an antagonist in hD(2L)-Low; a low intrinsic activity partial agonist in hD(2S)-Low; a moderate partial agonist in hD(3)-Ser-9 and hD(3)-Gly-9; a robust partial agonist in hD(2L)-High; and a full agonist in hD(2S)-High. Amisulpride, sulpiride and perphenazine behaved as preferential antagonists; and chlorpromazine and asenapine behaved as modest preferential antagonists; whereas fluphenazine, haloperidol, and blonanserin behaved as non-preferential antagonists in hD(2S)-Low and hD(2S)-High compared to hD(3)-Ser-9 and hD(3)-Gly-9. These findings may help to elucidate the basis of therapeutic benefit observed with these drugs, with varying mechanisms of action, in the treatment of Parkinson's disease, depression and schizophrenia.

PMID 21658377
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PubMedYakugaku zasshi : Journal of the Pharmaceutical Society of Japan2010-10-12

[Dopaminergic neuroprotection and reconstruction of neural network tiara].

Kitamura Yoshihisa Y

Parkinson's disease (PD) is an age-related neurodegenerative disorder in whose brain massive loss of dopaminergic neurons and formation of Lewy bodies occur in the substantia nigra (SN). L-Dihydroxyphenylamine (L-DOPA) substitution is still considered the gold standard of antiparkinsonian drug therapy. However, there has been little information available on neuroprotective and regenerative therapies. Recently, we have found that pramipexole and talipexole (D(2)/D(3)-dopaminergic agonists) inhibit dopaminergic neurotoxin-induced production of reactive oxygen species and apoptotic cell death. In addition, treatment with these drugs induces enhancement of anti-apoptotic Bcl-2 expression and inhibition of α-synuclein aggregation. Interestingly, recent study suggests that pramipexole treatment delays the progression of early PD symptom. On the other hand, we investigated the transplantation strategy for PD by assessing whether double-transplants of mouse embryonic stem (ES) cell-derived neurons in the striatum (ST) and SN, or subthalamic nucleus (STN), induce functional recovery in rat hemi-parkinsonian model. The study indicates that both the involvement of ST as a place of transplantation and the number of ES cell-derived neurons are essential factors for efficacy on PD animal model. Interestingly, an invertebrate planarian can regenerate complete organs, including a well-organized central nervous system (brain), within about 7 days. The regeneration process of the planarian dopaminergic neural network (tiara) may be divided into five steps: 1) anterior blastema formation, 2) brain rudiment formation, 3) brain pattern formation, 4) the formation of dopaminergic tiara, and 5) functional recovery of dopaminergic motor regulation, with several kinds of genes and molecular cascades acting at each step.

PMID 20930477
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