PubMed · 12152121
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
E Greco, P Polonio-Balbi, J C Speranza. 2002. Levosulpiride: a new solution for premature ejaculation?. https://doi.org/10.1038/sj.ijir.3900901
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of 1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the affinities and selectivities for all the dopamine receptor subtypes. The 'serotonin-derived' 3-oxygenated target compounds but not the 11-oxygenated analogues were superior to the unsubstituted LE 300. 11-Methoxy-7,14-dimethyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2-f][3]benzazecine (3e) was found to be the most potent antagonist at D2/D3/D4 and D5 receptor subtypes (Ki for D5 = 0.23 nmol) of all known benz-indolo-azecines.
Metoclopramide, the only drug approved by the FDA for treatment of diabetic gastroparesis, but used off-label for a variety of other gastrointestinal indications, has many potentially troublesome adverse neurologic effects, particularly movement disorders. In this article, we comprehensively review the indications and side effects of metoclopramide, and describe some common pitfalls and strategies to minimize the medicolegal risks to the prescribing physician. Metoclopramide accounts for nearly a third of all drug-induced movement disorders, a common reason for a malpractice suit. The entire spectrum of drug-induced movement disorders, ranging from subtle to life-threatening, can ensue from its use; akathisia and dystonia are generally seen early in the course of metoclopramide-induced movement disorders, whereas tardive dyskinesia and parkinsonism seem to be more prevalent in chronic users. Female sex, age and diabetes are the major risk factors for metoclopramide-induced movement disorders. It is therefore incumbent on gastroenterologists and other prescribing physicians to become familiar with the adverse neurologic effects associated with the use of metoclopramide, and to take appropriate preventive and defensive measures.
Gastrointestinal promotility drugs stimulate smooth muscle contractions to enhance gastric emptying and small and large bowel transit. Currently available drug classes with prokinetic properties include antidopaminergic agents, serotonergic agents, and motilin-receptor agonists. Due to moderate prokinetic effects, poor symptomatic responses and the presence of adverse effects, there is a clear need for new classes of prokinetics. Several newer prokinetic drugs and drug classes are currently under evaluation. Selecting candidate agents and designing the appropriate therapeutic trials is hampered by the lack of insight in the pathophysiology of motility-related symptoms. As gastrointestinal motor disorders are chronic, relapsing, and remitting disorders, it seems desirable that studies with candidate prokinetic drugs establish a long-term efficacy and not only short-term effects on gastrointestinal functions.