Agonist thụ thể nicotinic alpha-7: những ứng viên tiềm năng mới cho điều trị bệnh tâm thần phân liệt

Psychopharmacology - Tập 174 - Trang 54-64 - 2004
Laura F. Martin1, William R. Kem2, Robert Freedman1
1Department of Psychiatry, Department of Veterans Affairs and University of Colorado Health Sciences Center, Denver, USA
2Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, USA

Tóm tắt

Gạn lọc cảm giác thính giác là một phép đo sinh học về khả năng kìm hãm phản ứng được kích thích đối với âm thanh thứ hai trong hai kích thích thính giác, và khả năng này bị suy giảm ở những người mắc bệnh tâm thần phân liệt. Những khiếm khuyết trong việc gạn lọc cảm giác liên quan đến sự suy giảm chú ý, và có thể góp phần vào các triệu chứng nhận thức và rối loạn cảm giác. Quá trình ức chế này, liên quan đến việc giải phóng acid gamma-aminobutyric (GABA) nhờ thụ thể nicotinic alpha7 được trung gian bởi các tế bào inerneuron trong hồi hải mã, đại diện cho một mục tiêu tiềm năng mới cho can thiệp trị liệu trong bệnh tâm thần phân liệt. Bài báo này sẽ xem xét nhiều bằng chứng có liên quan đến hệ thống thụ thể nicotinic-cholinergic, và cụ thể hơn là thụ thể nicotinic alpha7 trong bệnh lý của bệnh tâm thần phân liệt và bằng chứng cho thấy các chất chủ vận thụ thể nicotinic alpha7 có thể cải thiện một số khiếm khuyết này. Việc suy giảm gạn lọc cảm giác thính giác đã được liên kết với gen thụ thể nicotinic alpha7 trên locus nhiễm sắc thể 15q14. Các biến thể đơn nucleotide trong vùng promoter của gen này thường xuất hiện nhiều hơn ở những người mắc bệnh tâm thần phân liệt. Mặc dù nicotine có thể đảo ngược tạm thời tình trạng gạn lọc cảm giác thính giác bị suy giảm ở những người mắc bệnh tâm thần phân liệt, nhưng hiệu ứng này mất đi khi ở mức độ mãn tính do sự nhạy cảm của thụ thể giảm. Clozapine có khả năng đảo ngược suy giảm gạn lọc cảm giác thính giác, có thể thông qua cơ chế thụ thể nicotinic alpha7, ở cả người và mô hình động vật với liều lượng lặp lại. Agonist thụ thể nicotinic alpha7 3-2,4 dimethoxybenzylidene anabaseine (DMXBA) cũng có thể tăng cường gạn lọc cảm giác thính giác trong các mô hình động vật. DMXBA được dung nạp tốt ở người và cải thiện một số chỉ số nhận thức. Các chất chủ vận thụ thể nicotinic alpha-7 dường như là các ứng viên hợp lý cho việc điều trị các rối loạn nhận thức và cảm giác trong bệnh tâm thần phân liệt.

Từ khóa

#Gạn lọc cảm giác thính giác #thụ thể nicotinic alpha7 #bệnh tâm thần phân liệt #chất chủ vận thụ thể nicotinic #lỗ nhiễm sắc thể 15q14

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