Citalopram HBr

Citalopram (Lu 10-171), a new bicyclic phthalane derivative, is an extremely potent inhibitor of neuronal serotonin (5-HT) uptake but has no effect on the uptake of noradrenaline(NA) and dopamine (DA) and no antagonistic activity towards 5-HT, histamine, gamma aminobutyric acid (GABA) and acetylcholine. It is an extremely specific and potent inhibitor of neuronal 5-HT uptake. Uptake mechanisms for other transmitter amines are not influenced by the drug^[1]. The SSRI citalopram has a greater effect on proliferation and a lesser effect on apoptotic activity. It affects cell cycle regulation by increasing proliferative potential and decreasing apoptotic activity in a site specific manner that may be indicative of hyperplasia. Citalopram alters FGF, MSX and TGFB expression in osteoblast cell culture^[3].

Cells are cultured in alpha minimum Eagles medium supplemented with 1% penicillin/streptomycin, 10% fetal bovine serum and Amphotericin B. For control data, cells are cultured for 3 or 7 days with standard alpha proliferation media. For SSRI treatments, media is supplemented with citalopram eluted to serially diluted doses between 10⁻⁴ mol through 10⁻¹⁰ mol to achieve a dose response curve.

Citalopram is devoid of cardiotoxic effects even when animals are exposed to concentrations far above the therapeutic level. In man citalopram is metabolized to compounds which are also potent 5-HT-uptake inhibitors without effect on noradrenaline(NA) uptake and which are found in lower concentrations than citalopram itself. Citalopram (1-16 mg/kg) stimulates the hind limb flexor reflex in the spinal rat. Citalopram potentiates 5-HT transmission~ possibly by producing very strong uptake inhibition without simultaneously blocking the post-synaptic 5-HT receptors^[1].