Abstract
Alaproclate, a specific inhibitor of neuronal serotonin re-uptake, was given to 12 patients with dementia of Alzheimer type. The drug was rapidly absorbed and an elimination half-life of 7.1±0.9 h (± SD, n=8) was calculated. Plasma protein binding for alaproclate was 82 ±1%. Two weeks of repeated administration produced plasma concentrations of alaproclate similar to those predicted from a single dose. The pharmacological effect of the drug was demonstrated by an inhibition of serotonin uptake in the patients' platelets and a reduction of the serotonin concentration in blood. Global rating of clinical efficacy showed a positive effect of alaproclate in five of the patients, mainly regarding emotional functions.
This is a preview of subscription content, log in via an institution to check access.
References
Andersen O, Johansson B, Svennerholm L (1981) Monoamine metabolites in successive samples of spinal fluid. Acta Neurol Scandinav 63:247–254
Arthur GR, Boyes RN, Bown D, Lundström J, Lindgren JE, McClure J, Scott DB (1980) Pharmacokinetics of alaproclate, a specific 5-HT uptake inhibitor. Abstract, World conference on clinical pharmacology and therapeutics, London, August 3–9
Benton J Sarah, Bowen DM, Allen Shelley I, Haan EA, Davison AN, Neary D, Murphy RP, Snowden Julie S (1982) Alzheimer's disease as a disorder of isodendritic core. Lancet no. 8269 I:456
Calil HM, Jostell K-G, Cowdry RW, Potter WZ (1982) Zimelidine and norzimelidine protein binding measured by equilibrium dialysis and cerebrospinal fluid. Clin Pharmacol Ther 31:522–527
Carlsson A, Adolfsson R, Aquilonius S-M, Gottfries C-G, Oreland L, Svennerholm L, Winblad B (1980) Biogenic amines in human brain in normal aging, senile dementia, and chronic alcoholism. In: Goldstein M et al. (eds) Ergot compounds and brain function, neuroendocrine and neuropsychiatric aspects. Advances in biochemical psychopharmacology, vol 23. Raven, New York, p 295
Gibaldi M, Perrier D (1975). Principle of superposition. In: Pharmacokinetics. Marcel Dekker, New York, pp 297–300
Heston LL, Mastri AR, Anderson VE, White J (1981) Dementia of Alzheimer type, clinical genetics, natural history, and associated conditions. Arch Gen Psychiatry 38:1085–1090
Kostowski W, Samanin R, Bareggi SR, Marc V, Garattini S, Valzelli L (1974) Biochemical aspects of the interaction between midbrain raphe and locus coeruleus in the rat. Brain Res 82:178–182
Lindberg UH, Thorberg S-O, Bengtsson S, Renyi AL, Ross SB, Ögren S-O (1978) Inhibitors of neuronal monoamine uptake. 2. Selective inhibition of 5-hydroxytryptamine uptake by α-aminoacid esters of phenethyl alcohols. J Med Chem 21:448–456
Marchbanks RM (1982) Biochemistry of Alzheimer's dementia: Short review. J Neurochem 39:9–15
Ögren S-O, Lindberg UH, Hall H (1980) Effects of alaproclate on the 5-HT mechanism in vivo: Evidence for regional selectivity. Abstract 12th CINP congress Gothenburg 1980
Ögren S-O, Holm A-C, Hall H, Lindberg UH (1983) Alaproclate: A new selective serotonin uptake inhibitor with a therapeutic potential in depression and senile dementia. J Neural Transm (in press)
Ross SB, Aperia B, Beck-Fries J, Jansa S, Wetterberg L, Åberg A (1980) Inhibition of 5-hydroxytryptamine uptake in human platelets by antidepressant agents in vivo. Ppsychopharmacology 67:1–7
Segal M (1979) Serotonerigc innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli. J Physiol 286:401–415
Syvälahti E, Eneroth P, Ross SB (1979) Acute effects of zimelidine and alaproclate, two inhibitors of serotonin uptake, on neuroendocrine function. Psychiatry Research 1:111–120
Triggs EJ, Nation RL (1975) Pharmacokinetics in the aged: A review. J Pharmacokin Biopharm 3:387–418
Yuwiler A, Plotkin S, Geller E, Ritvo ER (1970) A rapid accurate procedure for the determination of serotonin in whole human blood. Biochem Med 3:426–436
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bergman, I., Brane, G., Gottfries, C.G. et al. Alaproclate: A pharmacokinetic and biochemical study in patients with dementia of Alzheimer type. Psychopharmacology 80, 279–283 (1983). https://doi.org/10.1007/BF00436170
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00436170