Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, Germany.
Expert Opin Pharmacother. 2023 May;24(7):863-871. doi: 10.1080/14656566.2023.2201374. Epub 2023 Apr 18.
Adenosine antagonism, i.e. of the A receptor, improves dopamine-sensitive motor behavior in patients with Parkinson's disease with oral levodopa-associated motor complications. Only the xanthine derivative istradefylline is currently approved in Japan and in the US. This compound easily crosses the blood-brain barrier and shows high affinity to A receptors.
This narrative review discusses the place of istradefylline in the current available drug portfolio for Parkinson's disease following a literature research in PubMed.
Istradefylline is safe and well tolerated. Its efficacy was pronounced, when patients were on a lower chronic oral levodopa regimen. Levodopa causes a homocysteine elevation, which reflects an impaired methylation potential. As a result, an upregulation of A receptor occurs and weakens the efficacy of istradefylline as modulator of dopamine effects on motor behavior in Parkinson's disease. This is the hypothetical reason why clinical trials failed, when patients were on a higher chronic levodopa regimen.A way out of this dilemma is to enable higher dosing of istradefylline and substitution of L-dopa with compounds, which do not influence the methylation capacity. Long-term trials may show these levodopa sparing and thus motor complications delaying effects of istradefylline.
腺苷拮抗剂，即 A 受体拮抗剂，可改善伴有口服左旋多巴相关运动并发症的帕金森病患者的多巴胺敏感运动行为。目前，只有黄嘌呤衍生物伊曲茶碱在日本和美国获得批准。这种化合物很容易穿过血脑屏障，对 A 受体表现出高亲和力。
本文通过在 PubMed 上进行文献检索，对伊曲茶碱在帕金森病现有药物组合中的地位进行了叙述性综述。
伊曲茶碱安全且耐受良好。当患者接受较低的慢性口服左旋多巴治疗方案时，其疗效显著。左旋多巴会导致同型半胱氨酸升高，这反映了甲基化能力受损。结果，A 受体上调，削弱了伊曲茶碱作为调节帕金森病多巴胺对运动行为影响的调节剂的功效。这就是临床试验失败的假设原因，因为当患者接受更高的慢性左旋多巴治疗方案时。解决这一困境的方法是增加伊曲茶碱的剂量，并将 L-多巴替换为不影响甲基化能力的化合物。长期试验可能会显示出伊曲茶碱对左旋多巴的节省作用，从而延迟运动并发症的发生。
