INDIANAPOLIS — Prozac. Viagra. Lipitor.

The names of these incredibly popular medicines don't have defined meanings. But millions of dollars are spent creating just the right sound and image.

Research shows letters with a hard edge like P, T or K convey effectiveness. X seems scientific. L, R or S provide a calming or relaxing feel. Z means speed.

Earlier this month, Indianapolis-based Eli Lilly and Co. came up with Effient as the name for its new heart drug. "I would call that a fairly bold name because Effient seems to be just a letter or two off from efficient," said Anthony Shore, global director of naming and writing at Landor Associates.

Drug companies often delve into a weird science that ties symbolism to letters or prefixes when they hunt for the next hot brand name. In the case of Prozac, the first syllable makes the speaker pucker up and push out a burst of air, which grabs attention and implies effectiveness, said Jim Singer, who is president of the branding firm Namebase and helped Lilly name the antidepressant.

The naming process isn't easy, or getting any easier. Regulatory guidelines are becoming more restrictive, and the brand market is more crowded. More than 14,000 new drug names were filed last year with the U.S. Patent and Trademark Office, a 23 percent increase from 2003, according to Thomson CompuMark, a trademark research firm. The Food and Drug Administration now reviews between 300 and 400 names each year.

"It's getting almost impossible to do," said Bob Lee, trade counsel for Lilly.

BIG MONEY AT STAKE

The payoffs, however, can be huge. Global pharmaceutical sales totaled $643 billion in 2006, according to IMS Health, which tracks prescription information. Lipitor, the world's best-selling drug, rang up more than $3 billion in sales during the third quarter last year.

But before a new drug earns its first dollar, companies must find a brand that works in many languages, passes U.S. trademark and FDA reviews, and proves unique in the European Union's 27 countries.

It can cost $250,000 to $500,000 to create and test the name, then a couple of million dollars more to shepherd it through trademark searches and regulatory reviews. The entire process can last up to three years.

Lilly's Lee said the hunt for the right brand generally starts with either the company or a contractor drawing up a list of hundreds of possibilities. He would not comment on Effient because the FDA is still reviewing it.

They try to keep the name within two or three syllables or under nine letters so people can pronounce and remember it, said Scott Piergrossi, creative director for the consulting firm Brand Institute Inc., which has tested thousands of brands for drugmakers.

"It can't be too intimidating in the look, the feel, the tone and the meaning itself to patients," said Brand Institute CEO James Dettore.

The name also must say something. That's where symbolism can help.

Lilly's brand for the erectile dysfunction drug Cialis is derived from ciel, the French word for sky.

It provides a smooth, fluid sound that offers a sense of intimacy, said Landor's Shore. In contrast, Pfizer Inc.'s Viagra evokes the power of Niagara Falls.

"I think Viagra really hits the bull's-eye on virility," Shore said.

Made-up words that rely only on this subconscious symbolism are not the top choice for drugmakers. They prefer a name that says something about the drug, like Allegra, which alludes to the allergy relief it provides. They also like brand names that use real words to convey meaning.

Dettore and Piergrossi point to the brand Invega for a Johnson & Johnson anti-psychotic. The word Vega, the brightest star in the constellation Lyra, is imbedded in it. Any imagery related to the stars or space carries a positive connotation.

"It almost offers the patient hope through the name," Piergrossi said.

LOTS OF SCRUTINY

All this deep thinking can amount to nothing if it doesn't pass regulatory and trademark muster.

That original list of hundreds of possible names gets whittled down to between 30 and 50 preferences, Lilly's Lee said. A screening process that looks for identical or near-identical names then eliminates more.

Ultimately, drugmakers want to produce about 10 names "that look like they have a chance to survive," he said.

Then serious screening starts. Companies scour trademark databases for each country in which they plan to sell the drug.

"If I clear a trademark in the U.S., there's no guarantee it's clear in Canada or Germany or Hong Kong," Lee said.

Companies send their final selections to the FDA and European regulators, where the brands undergo more scrutiny.

One big taboo: The name cannot make a claim about a drug. The hair-loss treatment Rogaine, for instance, was originally called Regain until the FDA rejected it.

The FDA also tests for safety. A name shouldn't resemble another brand too closely. That can cause confusion with messy handwriting on a prescription.

Regulators will send the name in both script and voice mail to some nurses, doctors or pharmacists to see what they think. They'll also come up with a pool of names that might be confused with the new brand and analyze what would happen if they were mixed up.

Drugmakers aim to use the same brand name in every market, but sometimes that doesn't work. Lilly calls an osteoporosis drug Forteo in most of the world but had to call it Forsteo in Europe because regulators thought it was too similar to a drug branded Fortum.

Companies must be prepared for setbacks. The FDA rejects 35 percent to 40 percent of the brands it reviews. In Europe, the rejection rate approaches 50 percent, Lee said.

But the result can be worthwhile. Prozac became Lilly's top-selling drug, with sales topping $2 billion before it lost patent protection in 2000. The brand name became so common it wound up in Webster's New World College Dictionary.

And that name had no basis in reality, said Namebase's Singer. "It's just a good-sounding word," he said.