Complementary effects of combination therapy are also important at other receptor sites. For example, it is possible that clozapine’s antiadrenergic actions may contribute to its atypical properties . This hypothesis is supported by elec-trophysiological studies showing that alpha1-blockade antagonizes an excitatory noradrenergic input on mesolimbic dopaminergic neurons, thereby reducing excessive dopaminergic firing . However, definitive evidence supporting this theory is lacking . Apart from possible therapeutic effects, alpha1-receptor blockade is associated with side effects such as dizziness, tachycardia and postural hypotension. However, with the consideration that schizophrenia is an etiologically diverse syndrome and that the proposed polypharmacy strategy is meant to augment the treatment of patients who are partially responsive by using a multireceptor binding agent, some alpha1-blockade may be warranted. buy ortho tri-cyclen

Similarly, although there is little direct evidence to support a histaminic pathophysiological component to schizophrenia, most multireceptor, atypical antipsychotics (clozapine, olanzapine, quetiapine) have high affinities for the H1 receptor . Excessive blockade of this receptor is associated with side effects such as sedation and weight gain. For this reason, it is recommended that the augmenting antipsychotic should have low affinity for this receptor site, such that the chosen combination therapy has minimal side effects.