Pharmacological evaluation of ifosfamide and its enantiomers in laboratory animals.

Some pharmacological properties of commercial racemic ifosfamide (Holoxan) and its D- and L-enantiomers were compared in experiments on mice and rats. Although values of acute toxicity and some results of subchronic treatment revealed better parameters of L-form in comparison to racemic mixture, distinct hepatotoxic effects and thrombocytopenia noted in the course of prolonged treatment seem to be the important factors limiting therapeutic usefulness of levorotatory form.

comparison of pharmacological properties of cyclophosphamide and its enantiomers.

Comparison of pharmacological properties of commercial racemic Cyclophosphamide and its D- and L-enantiomers was performed in experiments on mice and rats. Acute toxicity, behavioral screening tests and the effects of subchronic treatment (influence on body mass, the increase of the mass of internal organs, mortality, morphology of peripheral blood, biochemical investigations of blood plasma, microscopic evaluation of liver and bladder) were taken into account. Summarized results revealed the most pronounced toxicity of D-cyclophosphamide.

Induction of wet dog shakes by intracerebroventricular bethanechol in rats. Antagonism by neurotransmitter receptor blockers.

Bethanechol chloride, administered intracerebroventricularly, induces a characteristic wet dog shake (WDS) response in rats in a dose-related manner. WDS induced by bethanechol at the dose of 100 micrograms was antagonized by atropine, scopolamine and spiperone (muscarinic cholinergic and dopaminergic antagonists, respectively), whilst metergoline, methysergide, phentolamine, propranolol and bicuculline (serotonergic, alpha-adrenergic, beta-adrenergic and GABA-ergic antagonists) fail to inhibit this effect. The present experiments show that the shaking response may be produced by bethanechol, a potent muscarinic agent administered by the intracerebral route, and suggest that bethanechol-induced shaking behavior in rats may be a useful animal model for delineating agents with antimuscarinic activity.