Therapeutic doses of antidepressants are projected not to inhibit human α4β2 nicotinic acetylcholine receptors.

Inhibition of central α4β2 nAChRs by antidepressants, proposed to contribute to their clinical efficacy, was assessed for monoamine reuptake inhibitors (amitriptyline, nortriptyline, fluoxetine, sertraline, paroxetine, citalopram) by comparing projected human unbound brain drug concentrations (Cu,b) at therapeutic doses with concentrations that inhibit human α4β2 nAChRs in vitro. Inhibitory concentrations (IC50) were determined by patch clamp and ranged from 0.8-3.

Microdialysis evaluation of clozapine and N-desmethylclozapine pharmacokinetics in rat brain.

A significant barrier to realization of the full potential of clozapine as a therapeutic agent in the treatment of schizophrenia is the substantial interpatient variability that exists along the therapeutic continuum of no response-efficacious response-adverse response. Genetic polymorphisms that manifest as highly variable pharmacodynamic and pharmacokinetic measures are its expected causes. To support investigations that seek to understand these causes, the plasma and central nervous system pharmacokinetics of clozapine were determined in rats, the latter using microdialysis sampling.

CB-1 receptors modulate the effect of the selective serotonin reuptake inhibitor, citalopram on extracellular serotonin levels in the rat prefrontal cortex.

A large percentage of depressed individuals use drugs of abuse, like cannabis. This study investigates the impact of cannabis on the pharmacological effects of the antidepressant citalopram. Using microdialysis in the prefrontal cortex of rats we monitored serotonin levels before and after cannabinoid (WIN55,212-2 or rimonabant) and citalopram administration.