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parkinsonism. Therefore, basic scientific andPaliperidone Extended Releaseclinical research on drugs that act at NMDA recep-A Viewpoint by Michael Davidsontors, as well as α-adrenergic, GABA, σ and other

Sackler School of Medicine, Tel Aviv University,classes of receptors are currently underway.Tel Aviv, Israel

In addition, a third line of investigation is toimprove the drug profile of dopamine receptorThe quest to improve the treatment of schizo-blockers by manipulating the drug delivery, thephrenia advances along several pathways. The mostpharmacokinetic and possibly the pharmacodynam-promising approach is to understand the aetiology or

the distal pathophysiology of this disease and to ic properties. Paliperidone extended release (ER)develop treatments based on this understanding. Un- belongs among this class of drugs. Phase III trialsfortunately, efforts in this direction are hampered by have demonstrated unequivocally that paliperidonethe disease heterogeneity, the poor definition of the

ER is more effective than placebo in amelioratingphenotype, the lack of an animal model and, mostly,

acute schizophrenia symptoms and maintaining re-by the presumed multi-factorial aetiology of schizo-mission. Dosages between 3 and 12 mg/day arephrenia. A simpler approach is to develop drugs thatgenerally well tolerated and there is no need fortreat the symptoms of schizophrenia without block-

ing dopaminergic receptors. This approach is driven titration, which may allow therapeutic dosage to beby two well established clinical realities. Firstly, the reached rapidly. Basic scientific data indicate thatefficacy of drugs that block dopamine receptors is the slow drug-release technology may provide anlimited to about two-thirds of the patients treated, advantage in terms of parkinsonism adverse effects,many of whom benefit only partially. Secondly,

although this is yet to be proven in phase IV clinicalmost, if not all, drugs that block dopamine receptorstrials, which are eagerly awaited. ▲cause some degree of akathisia and other frank