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Keywords:

  • paroxetine;
  • selective 5-HT uptake inhibition;
  • animal pharmacology.

ABSTRACT

Animal studies show that paroxetine is a potent and selective inhibitor of 5-hydroxytryptamine (5-HT) neuronal uptake. It shows excellent activity after oral administration, and pharmacological studies on its principal metabolites indicate that they are much less active than the parent compound. Paroxetine possesses no overt sedative or antihistaminergic properties and it does not potentiate the effects of alcohol. Weak activating properties are observed in EEG studies in animals at doses generally greater than those required to inhibit 5-HT uptake in the CNS, and the activated EEG in rats is associated with slight locomotor stimulation. However, specific studies indicate that this activation is not amphetamine-like. Paroxetine does not inhibit monoamine oxidase in vitro. Paroxetine is well tolerated by the cardiovascular system, being qualitatively and quantitatively less cardiotoxic than amitriptyline. The weak affinity of paroxetine for muscarinic cholinergic receptors in vitro is associated with mydriasis in vivo, but only at doses well in excess of those required to potentiate the effects of 5-HT in the CNS. It is therefore concluded that paroxetine should be an effective antidepressant with a reduced propensity to induce the adverse events that are characteristic of the tricyclic class of antidepressants.