PMID- 11402632
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20190826
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 41
IP  - 6
DP  - 2001 Jun
TI  - Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous 
      system.
PG  - 636-44
AB  - Antimuscarinic compounds are increasingly used to treat the symptoms of 
      overactive bladder; however, their use is often restricted by peripheral adverse 
      effects (AEs). On the other hand, data regarding their influence on the central 
      nervous system (CNS) are limited. This randomized, single-blind, parallel-group 
      quantitative-topographical EEG (qEEG) study of clinical phase I investigates the 
      potential CNS adverse effects of the three antimuscarinic drugs--tolterodine, 
      oxybutynin, and trospium chloride--in comparison to placebo. Overall, 4 x 16 
      (total 64) young, healthy male volunteers were included in the study. The 
      subjects were given either placebo or the clinically recommended daily doses of 
      the drugs dispensed in three doses on a single day (tolterodine 2 mg bid and once 
      placebo, total 4 mg/d; oxybutynin 5 mg tid, total 15 mg/d; and trospium chloride 
      15 mg tid, total 45 mg/d). The qEEG was recorded prior to and up to 4 hours after 
      each intake of the trial medication (a total of 10 qEEG sessions) under three 
      different conditions: at rest with eyes open, eyes closed, and under mental 
      demand. The drug tolerability was subjectively evaluated by the volunteer and the 
      investigator. In comparison to placebo (10% confidence interval), tolterodine and 
      trospium chloride did not induce changes of the qEEG power in five of the six 
      frequency bands (i.e., delta, alpha 1, alpha 2, beta 1, and beta 2). Isolated 
      power decreases were only observed in the theta frequency band. In contrast, 
      oxybutynin caused significant power reductions in four frequency bands (theta, 
      alpha 1, alpha 2, and beta 1; p < 0.01). The subjectively evaluated drug 
      tolerability was comparable between all treatment groups, although differences in 
      the AE occurrence existed, with the AE frequency being higher in the oxybutynin 
      group. The results of this study support the findings that oxybutynin as a 
      tertiary amine crosses the blood-brain barrier, causing significant qEEG activity 
      changes and more pronounced central adverse effects. Although tolterodine is also 
      a tertiary amine, it shows limited effects on qEEG activity (i.e., slight theta 
      power reductions), comparable to the effects of trospium chloride, a quarternary 
      amine, which barely crosses the blood-brain barrier. The minimal qEEG changes 
      observed with tolterodine and trospium chloride reflect most probably a rebound 
      message from the peripheral target organs. Prescription of oxybutynin thus 
      implicates a higher risk of CNS side effects.
FAU - Todorova, A
AU  - Todorova A
AD  - Pro Science Private Research Clinic GmbH, Kurt-Schumacher-Str. 9, D-35440 Linden, 
      Germany.
FAU - Vonderheid-Guth, B
AU  - Vonderheid-Guth B
FAU - Dimpfel, W
AU  - Dimpfel W
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Benzilates)
RN  - 0 (Cresols)
RN  - 0 (Mandelic Acids)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nortropanes)
RN  - 0 (Parasympatholytics)
RN  - 0 (Placebos)
RN  - 1E6682427E (trospium chloride)
RN  - 33RU150WUN (Phenylpropanolamine)
RN  - 5T619TQR3R (Tolterodine Tartrate)
RN  - K9P6MC7092 (oxybutynin)
SB  - IM
CIN - J Urol. 2005 Aug;174(2):588-9. PMID: 16006905
MH  - Adult
MH  - Benzhydryl Compounds/adverse effects/*pharmacology
MH  - Benzilates
MH  - Central Nervous System/*drug effects/physiology
MH  - Cresols/adverse effects/*pharmacology
MH  - Electroencephalography/methods
MH  - Humans
MH  - Male
MH  - Mandelic Acids/adverse effects/*pharmacology
MH  - Muscarinic Antagonists/adverse effects/*pharmacology
MH  - Nortropanes/adverse effects/*pharmacology
MH  - Parasympatholytics/adverse effects/pharmacology
MH  - *Phenylpropanolamine
MH  - Placebos
MH  - Tolterodine Tartrate
EDAT- 2001/06/14 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/06/14 10:00
PHST- 2001/06/14 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/06/14 10:00 [entrez]
AID - 10.1177/00912700122010528 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2001 Jun;41(6):636-44. doi: 10.1177/00912700122010528.