The meeting was extraordinary as board members Gerald Poje, Isadore Rosenthal, and Andrea Kidd Taylor released a lengthy series of internal directives that demonstrated a long-running management dispute between themselves and Hill. In laying out the scenario, Poje said the board had actively sought power from Hill for nearly a year. The meeting also presented a grim view of CSHIB's ability in its brief history to meet its charge of searching for the causes of chemical accidents. Although created in 1990, the board only received an operating budget in November 1997. It began with great gusto, investigating numerous deadly industrial accidents involving chemicals. However, only three accident reports have been released and eight remain outstanding. Of those eight, at best two may be released in the next year, more than two years after the accidents occurred, says J. Patrick Conlon, acting director of investigations. He did not discuss the status of other reports. Conlon was sitting in for the investigations director, who was fired by Hill. The slot remains open. A detailed investigation schedule will be issued when the board meets on Jan. 10, Poje said, adding that the board intends to hold monthly public meetings. Despite the difficulties, labor, environmental, and industry groups, including the Chemical Manufacturers Association, voiced support for the board and urged a quick resolution of its problems. JeffJohnson
Newly found opioid antagonist may aid function, drug studies The three classical opioid nervous system receptors (u, 8, and K) have powerful functional roles—as sites of action for narcotic painkillers, for example. So the 1994 discovery of a fourth opioid receptor and the identification in 1995 of the natural ligand that binds to it generated considerable excitement in the scientific community. Since then, researchers have been trying to determine the function of the new receptor, called opioid receptorlike 1 (ORL1), and its ligand. But their studies have been hampered by the lack of a potent and selective antagonist that could turn the receptor off.
Cancer Center, New York City. 'These include morphine, codeine, oxycodone, hydrocodone, methadone, demerol, and even heroin. Thus, this family of receptors is, without doubt, the most important target in the treatment of pain. The opiates are capable of eliminating pain that other classes of drugs cannot touch. ComAntagonist finders (from left) Iwasawa, Kawamoto, and Ozaki. mercially, this family Chemists Yoshikazu Iwasawa and of drugs has been extraordinarily successHiroshi Kawamoto, biochemist Satoshi ful." The work by Iwasawa and coworkers Ozaki, pharmacologist Hisashi Ohta, now enables "a wide range of studies to and coworkers at Banyu Tsukuba Re- more fully explore the pharmacology of search Institute, Tsukuba, Japan, have the ORL1 receptor," Pasternak says, and now found the first such antagonist [/. could lead to the discovery of new drugs Med. Chew., 4 2 , 5061 (1999)]. The in- that interact with that receptor. stitute is a unit of Banyu PharmaceutiResearch Director Jean-Claude cal, Tokyo, a subsidiary of Merck. Meunier of the Institute of Pharmacology Iwasawa and coworkers identified & Structural Biology, Toulouse, France, the small-molecule antagonist—a 2-oxo- says: "Obviously, J-113397 is an exciting tool that will help pharmacologists to confirm that the numerous reported physiological actions of nociceptin/orphanin FQ are indeed ORL1 receptor mediated, to identify new ones, and perhaps to dis" N v JVI' cover new receptors." Meunier's group codiscovered ORL1 and its ligand. Researcher Rainer K. Reinscheid of O OH the department of pharmacology at the J-113397 University of California, Irvine—who, with UC Irvine pharmacology professor Olivier Civelli and coworkers, codiscovbenzimidazole derivative called ered the endogenous ligand—says the J-113397—by chemical modification of a new antagonist will help scientists "decilead compound they had identified in a pher the functions of endogenous nocidrug-screening protocol. In in vitro ceptin/orphanin FQ [and determine] if tests, J-113397 bound to ORL1 with high antagonists or agonists could be useful potency and high selectivity. And in a therapeutic agents in the treatment of preliminary study, the researchers human diseases such as chronic pain, found the compound exhibits similar anxiety, or cardiovascular regulation." properties in vivo. Stu Borman Pharmacological studies had already shown that ORLl's endogenous ligand (nociceptin/orphanin FQ) is involved in a broad range of activities—from pain response, locomotion, neuroendocrine secretion, stress, and anxiety to learning and memory—suggesting that ORLl-tar- A class-action lawsuit filed last week in geted drugs might exhibit a similarly U.S. District Court for the District of Cowide spectrum of effects. lumbia alleges that Monsanto and other "Virtually all potent painkillers act life sciences and seed companies through one of the classical opioid recep- formed a "global cartel" that fixed prices tors," says opioid-receptor specialist on genetically modified seeds and conGavril W. Pasternak of the department of spired to restrain trade in corn and soyneurology at Memorial Sloan-Kettering bean markets.
o Y
Monsanto sued over gene-modified crops
DECEMBER 20,1999 C&EN 7
