An LC-MS method was developed for benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP), constituents of "party pills" or "legal herbal highs," and their metabolites in human blood plasma. Compounds were resolved using a mixture of ammonium formate (pH 4.5, 0.01 M) and acetonitrile (flow rate of 1.0 mL/min) with a C18 column. Calibration curves were linear from 1 to 50 ng/mL (R(2) > 0.99); the lower limit of quantification (LLOQ) was 5 ng/mL; the accuracy was >90%; the intra- and interday relative standard deviations (R.S.D) were <5% and <10%, respectively. Human plasma concentrations of TFMPP were measured in blood samples taken from healthy adults (n = 6) over 24 h following a 60-mg oral dose of TFMPP: these peaked at 24.10 ng/mL (±1.8 ng/mL) (C(max) ) after 90 min (T(max)). Plasma concentrations of 1-(3-trifluoromethyl-4-hydroxyphenyl) piperazine peaked at 20.2 ng/mL (±4.6 ng/mL) after 90 min. TFMPP had two disposition phases (t(½) = 2.04 h (±0.19 h) and 5.95 h (±1.63 h). Apparent clearance (Cl/F) was 384 L/h (±45 L/h).
Background
: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor
(BDNF)
Val
66
Met; a single-nucleotide polymorphism (SNP) implicated in memory function.
Methods
: Participants were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-
like
enhancements of the visually-evoked response, and a test of visual memory.
Results
: The magnitude of LTP 40 min after induction was predictive of long-term memory performance. Additionally, the
BDNF
Met allele was associated with both reduced LTP and reduced memory performance.
Conclusions
: The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.
Fluorophenylpiperazine, methoxyphenylpiperazine, chlorophenylpiperazine, methylbenzylpiperazine and methylenedioxybenzylpiperazine had significant inhibitory effects on CYP2D6, CYP1A2, CYP3A4, CYP2C19 and CYP2C9 isoenzymes but each piperazine had a different inhibitory profile. The metabolic interaction between BZP and TFMPP may have clinical implications, as these agents are often combined in 'party pills'.
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