Preliminary evaluation of besipirdine for the treatment of Alzheimer's disease. Besipirdine Study Group.
Besipirdine hydrochloride (HP 749) is an indole-substituted analog of 4-aminopyridine. Besipirdine enhances both cholinergic and adrenergic neurotransmission in the central nervous system, and may have greater efficacy than purely cholinergic agents in treating dementia due to Alzheimer's disease. The present study examined the efficacy and tolerability of two doses of besipirdine (5 and 20 mg BID) in 275 patients with Alzheimer's disease during 3 months of treatment and during 3 months after withdrawal of treatment. Besipiridine was generally well tolerated. The level of performance on a cognitive test was sustained during 3 months of treatment with besipirdine, whereas the performance of patients treated with placebo deteriorated over the same time period. The results suggest a dose-response relationship, with greater efficacy after 3 months of treatment and longer persistence after treatment withdrawal for besipiridine 20 mg BID than for 5 mg BID. A clinical global rating did not detect a besipirdine treatment effect. The full efficacy after 3 months of treatment did not persist after withdrawal of treatment, suggesting that the benefit is primarily symptomatic. Treatment with higher doses and for longer periods may enhance efficacy on both cognitive and clinical global assessments.
Huff
F J
FJ
Hoechst-Roussel Pharmaceuticals Inc., Somerville, New Jersey 08876, USA.
D000544:Alzheimer Disease / Q000188:drug therapy*; D003863:Depression / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007211:Indoles; D011725:Pyridines; C074872:besipirdine