Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions; new chemical compounds, including immunotherapies; and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders. Furthermore, advancements in the understanding of the genetic and epigenetic basis of drug addiction and the pharmacogenetics of the safety and/or efficacy of the medications are providing opportunities for more individualized pharmacotherapy approaches.
The effects of oral administration of clonazepam, a new benzodiazepine derivative (F. Hoffmann-La Roche), on the central nervous system were compared with those of diazepam and several anticonvulsants in mice and rats. 1) Clonazepam exhibited a moderate inhibitory effect on the locomotor activity observed with open-field situation in mice and no effect in rats, while it inhibited markedly the rearing behavior in both animals, the duration of action being approximately six hours.
Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its effect on the central nervous system (CNS) was studied. 1. When orally administered in mice, beraprost sodium at 0.3 mg/kg caused a flush of skin, a suppression of spontaneous motility, and a fall of body temperature.
The effects of 1-[2-[bis (4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl) piperazine dihydrochloride (I-893) on the central nervous system were behaviorally and electroencephalographically investigated. Intraperitoneally injected I-893 (5-10 mg/kg) dose-dependently increased spontaneous motor activity in mice, but repeated injections did not affect the increase in the locomotor activity. In reserpinized mice, spontaneous motor activity was not increased by oral I-893.
Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-gp, MRP, BCRP in conjunction with metabolizing enzymes (CYPs) are major factors in such interactions. Most effective combination antiretrovirals (ARV) therapy includes a PI or a NNRTI or two NRTI. Coadministration of such ARV may induce efflux transporters and/or CYP3A4 resulting in sub-therapeutic blood levels and therapeutic failure due to reduced absorption and/or increased metabolism.
Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as on that of their caregivers. However, effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD, such as aggression, agitation, irritability, and hallucinations, in a randomized, single-blind, placebo-controlled study.