Update on Medications in Schizophrenia

Antipsychotics are a pharmacologically heterogeneous group of compounds, but all act as D2 dopamine receptor antagonists, an action linked to their antipsychotic effect. Today, sixty years on since 1952, we have the FGAs and the SGAs. These medications continue to be useful, and continue to have some troubling adverse effects. As a class, the FGAs are more likely to be associated with EPS but this is primarily true of medications that bind tightly with D2 neuroreceptors, such as haloperidol, and less true of medications that bind weakly, such as chlorpromazine. Anticholinergic effects are especially prominent with weaker-binding FGAs, as well as with the SGA clozapine. As a class, the SGAs, especially clozapine and olanzapine generally tend to cause more problems relating to the metabolic syndrome, such as obesity and type 2 diabetes mellitus. All antipsychotic medications are associated with an increased likelihood of sedation, sexual dysfunction, postural hypotension, prolonged QT interval and sudden death. Primary care physicians need to be familiar with the individual adverse effect profiles of these medications.

Development of natural products as drugs acting on central nervous system

We have recenty studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor.