ANTIDEPRESSANT'S SPEED EXPLAINED - C&EN Global Enterprise

Aug 23, 2010 - Depression is believed to correlate with a reduction in the number of synapses, or connections between neurons, in the prefrontal corte...
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NEWS OF THE WEEK

POTASHCORP SNUBS BHP BILLITON FERTILIZERS: Both companies see

a bright future for crop nutrients but can’t agree to a takeover deal

acquisition offer of Australia’s BHP Billiton, and now the mining giant is taking its bid for the fertilizer company directly to shareholders. The offer “provides PotashCorp shareholders with value certainty and an immediate opportunity to realize the value of their shares in the face of volatile equity markets,” BHP Billiton’s chairman, Jacques Nasser, wrote to PotashCorp’s board. In a conference call with investors, PotashCorp CEO William J. Doyle gave a rebuttal. “We believe we are on the verge of an inflection point where potash demand is expected to return to historical trend line growth and tightened supply and improved pricing,” he said. PotashCorp’s board unanimously rejected BHP Billiton’s $130.00-per-share POTASHCO RP

A PotashCorp mine in Saskatchewan.

P

OTASHCORP HAS REJECTED the $40 billion

ANTIDEPRESSANT’S SPEED EXPLAINED NEUROSCIENCE: Ketamine stimulates

synapse formation within hours

CH3 NH Cl Ketamine

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NLIKE COMMERCIALLY available antidepres-

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sants, which require weeks or months to take effect, a single dose of ketamine can overcome depression in hours, an advantage that can spell the difference between life and death for suicidal patients. Researchers at Yale University School of Medicine have now discovered why the compound works so fast. Their findings illuminate the mechanisms underlying depression and also suggest new targets for its treatment. Depression is believed to correlate with a reduction in the number of synapses, or connections between neurons, in the prefrontal cortex of the brain, notes Ronald S. Duman, who studies molecular psychiatry and pharmacology at Yale. Duman’s team now reports that ketamine undoes this damage by increasing the number of these synapses in rats within 24 hours of administration, whereas traditional treatments do not (Science 2010, 329, 959). The researchers determined that ketamine stimuWWW.CEN-ONLINE.ORG

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offer, maintaining that it “grossly undervalues” the company. The offer represents a 16% premium of its stock price on Aug. 16, the day before the offer was disclosed to the public. In mid-2008, when the fertilizer industry peaked before the financial downturn, PotashCorp stock was trading at more than $200 per share. On Aug. 17, PotashCorp shares immediately jumped to more than $140 on news of the offer, an indication that shareholders are anticipating a better deal than BHP Billiton’s tender offer. Analysts also are anticipating a bid that is better than the initial $130.00-per-share offer. After BHP Billiton’s acquisition bid, David Begleiter, a stock analyst at Deutsche Bank, raised his target price for PotashCorp to $150.00 per share to reflect what he believes is the “minimum acquisition price,” and he wouldn’t rule out offers climbing as high as $175.00 per share. PotashCorp is the world’s largest producer of potash, which contains potassium compounds that enhance root growth in crops such as corn and soybeans. The firm generated net income of $1.0 billion on $4.0 billion in sales in 2009. BHP Billiton mines for metals such as aluminum, copper, lead, zinc, gold, silver, iron, and titanium. It also has diamond and coal mines and an oil and gas exploration business. The company has been keen on entering the potash business and recently acquired a large land position in PotashCorp’s backyard in Saskatchewan, where it has been planning a new potash mine.—ALEX TULLO

lates the mammalian target of rapamycin (mTOR) signaling cascade, which is involved in protein synthesis and synaptic modification in neurons. Ketamine activates this pathway by preventing the neurotransmitter glutamate from binding to the N-methyl-d-aspartate (NMDA) class of receptors on neurons. “Together, these findings suggest that the rapid activation of mTOR-mediated signaling pathways may be an important and novel strategy for the rational design of fast-acting antidepressants,” note John F. Cryan and Olivia F. O’Leary, neuropharmacologists at University College Cork, in Ireland, in a commentary about the work (Science 2010, 329, 913). They add that drugs that target this pathway would provide an alternative to the antidepressants currently on the market, nearly all of which function by boosting brain levels of neurotransmitters such as serotonin and norepinephrine. Ketamine itself is unsuitable as a commercial antidepressant. At doses higher than what is required for the antidepressant effect, it serves as an anesthetic. It can induce hallucinations—hence its popularity as the street drug “Special K”—and it must be injected. Ketamine can be administered by a doctor, but this practice is inconvenient because the antidepressant effect of a dose wears off after about a week. The pharmaceutical industry is now trying to develop safe, fast-acting antidepressants that can be given orally and can’t be abused, says Duman.—SOPHIE ROVNER

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