Biomedical subjects
Publications and source records attributed to Christine E Heading.
Vivitrex, an injectable, sustained-release formulation of the opioid antagonist naltrexone, is being developed by Alkermes and Cephalon for the potential once-monthly treatment of alcoholism and opiate use disorder. Alkermes and Cephalon are currently awaiting Food and Drug Administration review of the Vivitrex new drug application, which was granted Priority Review in May 2005.
The venoms from Conus snails are rich in peptides with potent specificity for mammalian receptor sites. Each venom typically contains up to 100 conopeptides, and with approximately 500 species of Conus snail, the number of active peptides is considerable. The receptor sites targeted appear to be mostly linked to ion channels, with voltage-gated, ligand-gated and G-protein linked sites identified. Both the central and peripheral nervous system present possible physiological targets for therapeutic products derived from the venoms, although the molecules in the most advanced development target the central nervous system. In turn, this presents problems of bioavailability, while the potency is a potential source of toxicity.
Pharmacotherapy for substance abuse is rarely offered to willing recipients without some form of psychosocial support. Pharmacotherapy must match the needs of the patient at the time it is offered, as patients often progress through one or more cycles of use and abstinence. Increasingly, long-acting formulations of agonists and antagonists are being developed as substitution or relapse-prevention products, respectively, in order to aid compliance. Products which target use-reinforcement pathways are starting to progress through clinical trials, as are vaccines that potentially prevent the abused substance reaching the brain. For cocaine abuse, the main focus is on products targeting the dopamine reuptake system.
Nabi Biopharmaceuticals is developing NicVAX, a proprietary vaccine designed as a potential therapeutic to prevent and treat nicotine addiction.
Conus peptides comprise a diverse class of bioactive molecules, each of which is believed to have a biological target. From the 50,000 plus molecules thought to exist, several groups are judged to have potential neuroprotective activity. Those that block voltage-gated calcium channels were seen as most promising, but this is now in some doubt. Those that act at NMDA receptors may be able to protect against acute and chronic assault, while those acting at nicotinic receptors or at potassium channels seem mainly to have potential against chronic assault. The poor pharmacokinetic profile of the peptides remains a challenge.
TA-CD (formerly IPC-1010), a cocaine conjugate that stimulates the production of antibodies against cocaine, is under development by Xenova (formerly Cantab) for the potential treatment of cocaine dependence [176912], [414867], [449997]. The vaccine was originally discovered at Stanford University and exclusively licensed to ImmuLogic Pharmaceuticals as IPC-1010 [176908]. It was renamed TA-CD when ownership was transferred to Cantab [463510], [463511]. By April 2002, a second phase IIa dose escalation trial was underway [445298], which was ongoing in September 2002 [463866].