Table 4.

Summary evaluation of the CNS penetration potential of various antimuscarinic agents relative to reported clinical CNS side effects

Antimuscarinic drug	Predicted CNS penetration potential, based on physicochemical properties	Measured permeability in vitro	Substrate of P-gp in vitro	Measured CNS penetration in rats in vivo	Observed clinical CNS side effects*
Trospium	Not significant	Low	Yes	Not significant	NR†
Fesoterodine (5-HMT)	Significant	Moderate	Yes	Not significant	NR‡
Darifenacin	Significant	High	Yes	Not significant	0.9–2.1% dizziness§
Solifenacin	Significant	High	No	Significant	1.8–1.9% dizziness¶
Tolterodine	Significant	High	No	Significant	3% somnolence**
					2% dizziness††
Oxybutynin	Significant	High	No	Significant	2–12% somnolence‡‡
					4–6% dizziness‡‡
					12.6% somnolence§§
					15.6% dizziness§§

^*Incidence of CNS adverse events in randomized controlled clinical trials, as reported in approved product labels.

^†Sanctura 20 mg twice daily and Sanctura XR 60 mg once daily.

^‡Toviaz 4 and 8 mg once daily.

^§Enablex 7.5–15 mg once daily.

^¶Vesicare 5 or 10 mg once daily.

^**Detrol LA 4 mg once daily.

^††Detrol 2 mg twice daily.

^‡‡Ditropan XL 5–30 mg day⁻¹ given once daily.

^§§Ditropan 5–20 mg day⁻¹ given three times daily.

NR: none reported by ≥1% (trospium) or ≥2% (trospium XR and fesoterodine) patients and exceeding placebo rates.