July 2009 Archives
Tue Jul 28 18:26:47 PDT 2009
The Molecule That May Have Killed Michael Jackson
The molecule above is called Diprivan or propofol, the drug that has been linked to the death of Michael Jackson.
Propofol does not possess pain reducing qualities; however it does rapidly induce unconsciousness, forgetfulness, and an extreme detachment from the physical world. Hence it is used medically as an anesthetic. It renders patients unconscious rapidly and once the patient is 'out' additional drugs are used to suppress their sensation of pain.
Although propofol is relatively easy to synthesize from common chemical building blocks, it is a difficult drug to self administer. To avoid rapid decomposition it must be injected into the body and the dosage needs to be finely monitored and finely controlled to prevent death by heart attack or by suppression of respiration. This combination of characteristics makes the risk reward ratio from a drug abuser's perspective very unattractive. Despite the fact that propofol is difficult to self administer there have been documented cases of the abuse of the drug and these cases have been generally limited to those with medical knowledge and medical access to the drug.
Analysis of the activity of a range of molecules which contain similar chemical features has led to detailed knowledge of the origin of the pharmacological effects of Diprivan.
The propofol molecule interacts with the gamma-aminobutyric acid type A, GABA(A), receptor. The keys to the binding interaction are the hydrophilic group at the center of the molecule (shown in red in the diagram above) and two hydrophobic centers which are on either side of the hydrophilic center.
The commercial development of the propofol molecule has focused on the control of its concentration in the human body. These developments have taken the form of the careful design of the formulation of the medical emulsion which is given intravenously to patients and more recently in designing pro-drugs which are metabolized in the body to yield free propofol molecules.