A tiny California start-up and the pharmaceutical arm of a big Dutch chemical company are joining forces in a bold bet that they can convert a newfound apparent sixth sense into a pathway to treat a variety of mood and other maladies.

Pherin Pharmaceuticals Inc., a closely held Menlo Park concern, said it signed an agreement with NV Organon, a unit of Akzo Nobel NV, to develop and market medicines based on a family of compounds discovered by Pherin that it says mimic pheromones. Pheromones are odorless chemical messages that some scientists believe affect such human functions as appetite and sexual motivation, as well as feelings of well-being.

If Pherin is right, the pact could lead to the development of a new class of drugs to treat such conditions as anxiety, overeating and premenstrual syndrome. The compounds also may be tested as a new form of birth control, says David Berliner, the former professor of anatomy who founded Pherin.

Some companies, including Fremont, Calif.'s Erox Corp., also founded by Dr. Berliner, already are marketing fragrances containing pheromones that are said to enhance sexual attraction. The new venture would be the first to develop synthetic versions of such compounds as drugs.

The Human Factor

But whether humans actually communicate with pheromones is in scientific dispute, and skeptics remain unconvinced that a sixth sense exists, at least in the fashion that Dr. Berliner describes.

Dr. Berliner says Pherin's compounds, dubbed vomeropherins, are sprayed in minute quantities into the nasal passages, where they trigger a response from a tiny, mysterious pit called the vomeronasal organ, or VNO, that he says sends messages directly to the brain. Scientists at Pherin and at the University of Utah have recently presented papers at meetings documenting the activity of the VNO and significant human responses to the effects of certain of the compounds.

Other researchers, however, have doubts about whether the VNO, which clearly works in some other animals, is functional in humans. Charles J. Wysocki, a neuroscientist at Monell Chemical Senses Center in Philadelphia, says scientists in Denmark and France have found that such a structure is present during prenatal development, when cells from the area in the nose migrate to a portion of the brain known as the hypothalamus and ultimately work to regulate hormones related to fertility. But once the migration occurs, this research suggests, the VNO structure begins to disintegrate, losing its function by birth.

"If it turns out that the fetal VNO disappears during [prenatal] development, then I'm hard-pressed to come up with a scenario that results in a functional VNO during adulthood," Dr. Wysocki says. He speculates that if people respond to the Pherin compounds, either something other than the VNO is at work or subjects in the company's experiments are influenced by the placebo effect.

Dr. Berliner disputes such challenges, saying his research group has documented responses in carefully designed tests in which research subjects were blinded as to whether they were getting a synthetic pheromone or a placebo. Some of the studies, he adds, indicate that the response is independent of the sense of smell, suggesting a sixth sense.

Still Nascent, but Attracting Money

In any event, officials at Organon are intrigued enough to support further development. The companies wouldn't disclose terms of the agreement or specify the compounds in which Organon is interested, but they indicated that the deal is structured much like other alliances in which large pharmaceutical makers pay small companies in installments based on progress toward the development of a marketable product. Dr. Berliner indicated that it probably would cost $150 million to bring one compound through regulatory approval to market.

Organon is a leading manufacturer of birth-control pills and other reproductivesystem medicines, as well as psychiatric drugs. "That is the link" to the company's interest in Pherin's compounds, says Eduard Hirschfeld, a spokesman for parent Akzo Nobel.

Dr. Berliner says the response to the vomeropherins is registered in the hypothalamus, the part of the brain that controls the production of hormones, regulates appetite and controls anxiety, among other functions. Partly because doses measured in tiny quantities called picograms are all that is necessary to trigger a response, and because the compounds aren't delivered systemically through the bloodstream, he believes they will be particularly safe and free of side effects.