However, despite extensive efforts to develop PDE4 inhibitors for CNS disorders, clinical success has been hampered by various issues, including poor brain penetration, suboptimal pharmacokinetics, and dose-limiting side effects, especially nausea and diarrhea (McDonough et al., 2020; Robic et al., 1999; Kang et al., 2023; Krause and Kühne, 1988; Sanftner et al., 2009). The gene discussed is PDE4A; the disease is central nervous system disorder.