Premium
Measurements of tacrine and monoamines in brain by in vivo microdialysis argue against release of monoamines by tacrine at therapeutic doses
Author(s) -
Baldwin H.A.,
Souza R.J.,
Sarna G.S.,
Murray T.K.,
Green A.R.,
Cross A.J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12357.x
Subject(s) - tacrine , microdialysis , dopamine , chemistry , monoamine neurotransmitter , in vivo , extracellular fluid , extracellular , pharmacology , endocrinology , medicine , serotonin , acetylcholinesterase , biochemistry , biology , receptor , microbiology and biotechnology , enzyme
1 The concentration of tacrine (tetrahydroaminoacridine or THA) in plasma, regions of brain and cerebral extracellular fluid has been studied in the rat at various times following injection of a dose of 5 mg kg −1 , i.p. 2 The peak plasma THA concentration was 2.46 nmol ml −1 , and occurred 30 min post injection and clearance was first order ( t 1/2 = 90min). The concentration in the brain peaked between 30–60 min, and was around 30 times plasma concentration (striatum peak concentration = 65 ± 3 nmol g −1 ). Extracellular cerebral concentration measured by in vivo microdialysis was similar to plasma concentration with the peak occurring 100 min post‐injection. 3 No evidence was obtained by in vivo dialysis for THA inducing dopamine release from striatum or 5‐hydroxytryptamine (5‐HT) release from the frontal cortex. Enhanced release of dopamine did occur after (+)‐amphetamine (5 mg kg −1 , i.p.) injection, while KCl (100 m m ) in the probe released both dopamine and 5‐HT. 4 Since the minimum plasma THA concentration achieved in this study was at least twice that found in the plasma of patients given THA for the treatment of dementia, these results suggest that monoamine release in the brain does not occur during therapy.