Codeine is an opiate used to manage mild to moderate pain severe enough to require an opioid. Codeine is a selective agonist for the mu opioid receptor and has an affinity to delta and kappa-opioid receptors. In some countries, this drug is regulated under various narcotic control laws, because its chronic use can cause physical dependence. In others, it is available without a medical prescription in combination with paracetamol.

Nebicapone (BIA 3-202) is a reversible, and tight-binding peripheral inhibitor of the enzyme catechol-O-methyltransferase (COMT) being developed for use as an adjunct to levodopa/dopa decarboxylase inhibitor in the treatment of PD. Nebicapone dose dependently and significantly decreased COMT activity. Nebicapone also increased systemic exposure to levodopa and improved motor response. The tight-binding nature of the inhibition produced by BIA 3-202 was evaluated by performing an Ackermann-Potter plot. The true K(i) for BIA 3-202, derived from the nonlinear regression analysis, was 0.19+/-0.02 nM. In substrate competition studies, an increase in the concentration of adrenaline resulted in a linear increase in IC(50) values for BIA 3-202.

Motesanib (AMG 706), a novel nicotinamide, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4 and Kit receptors. Motesanib was expected to reduce vascular permeability and blood flow in human tumours. A phase III trial of motesanib in combination with paclitaxel and carboplatin in non-squamous NSCLC has been terminated by Takeda and subsequently the development was discontinued. Motesanib has also been investigated up to phase II in breast, thyroid, colorectal and gastrointestinal stromal tumours. However, development has been discontinued in these indications.

Licofelone (ML 3000) is a pyrrolizine derivative originally discovered by Merckle GmbH and developed by EuroAllaince with a unique pharmacological profile, which comprises optimal gastrointestinal tolerability and high analgesic and anti-inflammatory activity. These effects are due to balanced and selective inhibition of both cyclo-oxygenase and 5-lipoxygenase. Inhibition of 5-lipoxygenase may reduce the gastrointestinal toxicity associated with other non steroidal anti-inflammatory drugs, which only inhibit cyclooxygenase. Licofelone also has antipyretic and antiaggregatory properties. Clinical and preclinical trials were also undertaken for osteoarthritis, rheumatoid arthritis, asthma, pain and inflammation. However, development for these indications appear to have been discontinued.