Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.
Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.
Askmark
H
H
Department of Neurology, University Hospital, Uppsala, Sweden.
Aquilonius
S M
SM
Gillberg
P G
PG
Hartvig
P
P
Hilton-Brown
P
P
Lindström
B
B
Nilsson
D
D
Stålberg
E
E
Winkler
T
T
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004576:Electromyography / Q000187:drug effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009460:Neurologic Examination; D011930:Reaction Time / Q000187:drug effects; D013619:Tacrine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D013619:Tacrine