Bockaert J, Claeysen S, Compan V, Dumuis A
UPR CNRS 2580-CCIPE, 141 rue de la Cardonille, 34094 Montpellier cedex 5, France.
Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):39-51. doi: 10.2174/1568007043482615.
Serotonin 4 receptors (5-HT(4)Rs) were discovered 15 years ago. They are coded by a very complex gene (700Kb, 38 exons) which generates eight carboxy-terminal variants (a, b, c, d, e, f, g, n). Their sequences differ after position L(358). Another variant is characterized by a 14 residue insertion within the extracellular loop 2. Highly selective potent 5-HT(4) receptor antagonists and partial agonists which cross the blood-brain barrier have been synthesized, but a specific full agonist for brain studies is still missing. Based on physiological and behavioral experiments, 5-HT(4)Rs may be targets to treat cognitive deficits, abdominal pain and feeding disorders. One 5-HT(4)R-directed drug (SL65.0155) is already in phase II to treat patients suffering from memory deficits or dementia.
血清素4受体（5-HT(4)Rs）于15年前被发现。它们由一个非常复杂的基因编码（700千碱基对，38个外显子），该基因产生八种羧基末端变体（a、b、c、d、e、f、g、n）。它们的序列在L(358)位置之后有所不同。另一种变体的特征是在细胞外环2内有一个14个残基的插入。已经合成了能够穿过血脑屏障的高选择性强效5-HT(4)受体拮抗剂和部分激动剂，但仍缺少用于脑研究的特异性完全激动剂。基于生理学和行为学实验，5-HT(4)Rs可能是治疗认知缺陷、腹痛和进食障碍的靶点。一种针对5-HT(4)R的药物（SL65.0155）已进入治疗记忆缺陷或痴呆患者的II期临床试验。
