Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with overactive bladder.
BACKGROUND
Muscarinic receptors in the brain play an important role in cognitive function, especially memory, and there is growing awareness that specific antimuscarinic drugs for overactive bladder (OAB) may have adverse central nervous system (CNS) effects. Selection of an antimuscarinic OAB drug with reduced potential for CNS effects could be especially beneficial in the elderly people, in whom even the modest cognitive impairment may negatively affect independence.


OBJECTIVE
The purpose of the study is to determine if trospium chloride is assay detectable in the CNS of older adults with OAB and to assess whether deterioration of memory occurs in these individuals.


METHODS
Twelve cognitively intact older adults (>or=65-75 years old) with OAB were given extended-release trospium chloride 60 mg once daily over a 10-day period to achieve plasma steady-state levels. Standardised memory testing (Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised) was performed predose and postdose. Cerebrospinal spinal fluid (CSF) and plasma samples were drawn on day 10 and assayed for trospium chloride. Predose (day 0) and postdose (day 10) results on the memory tests were compared using a reliable change index to assess a meaningful change in learning or memory.


RESULTS
Trospium chloride levels in all the CSF samples (n = 72) of all participants were assay undetectable (<40 pg/ml) on day 10 at steady-state peak plasma concentration concurrent with measureable peak plasma values (C(max) = 925 pg/ml). Repeat memory testing revealed no significant net drug effect on learning or recall.


CONCLUSIONS
This is the first study to investigate for the presence of an OAB antimuscarinic in the human brain, performed by assaying for concentrations of trospium chloride and correlating with simultaneous clinical cognitive safety measures. The results of both pharmacological and neuropsychological testing support the hypothesis of a lack of detectable CNS penetration for the quaternary amine trospium chloride.
Staskin
D
D
Caritas-St Elizabeth's Medical Center, Division of Urology, Tufts University School of Medicine, Boston, MA 02135, USA. staskinatt@gmail.com
Kay
G
G
Tannenbaum
C
C
Goldman
H B
HB
Bhashi
K
K
Ling
J
J
Oefelein
M G
MG
D000368:Aged; D001561:Benzilates; D002490:Central Nervous System / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D018727:Muscarinic Antagonists / Q000009:adverse effects* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D009483:Neuropsychological Tests; D009662:Nortropanes / Q000009:adverse effects* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
D001561:Benzilates; D018727:Muscarinic Antagonists; D009662:Nortropanes; C003330:trospium chloride