Wired for Sex
by Paulina Borsook
Back to paulinaborsook.com

 

 

Viagra And His Brethren: Fairy Tales Can Come True

The last pill jar was a deep red, also appeared to be antique, with silver scrollwork and a silver stopper. Eighteen blue, diamond-shaped pulls, with a brand name on one side and the inscription "VGR50".

"Anybody know what this is?" I held one out in my hand.

"Hang onto it, Houseman," said Hester, with a grin.

"You may need it a bit sooner than you think."

I bit, I admit it. From her comment, I sort of assumed it might have something to do with Alzheimer's, or something like that.

"Memory stimulant?"

"Probably, in your case, that would be all it is,", she said, laughing.

"It's Viagra, Houseman."

"Oh."

I put it back.

"Hey, I'm sorta proud I didn't know what it was."

"That's the memory part," she said.
Code Sixty-One Donald Harstad (Doubleday 2002)

The VGR50 mentioned in this policier set in rural Iowa belonged to a sociopath who bamboozled the coterie of young people around him into thinking he was a vampire. Fictional villain Daniel Peel was charismatic and stylish and athletic, and part of how he induced his followers into thinking he really was a supernatural being was his ability to engage in multipartner orgiastic sex for hours on end. To engage his followers in this magnificent Darkside con, he relied on methamphetamine home-brewed from batteries --- and Viagra.

But Viagra -really- is something like the supernatural come to life. In every culture and every era, there has been the search and the hope for an anti-impotence potion. And now, thanks to serendipity attaching itself to pharmaceutical company Pfizer (chance really does favor the trained mind), the stuff of fairy tales has been made real. The very fact of the existence of Viagra, a drug that really does provide a temporary fix for erectile dysfunction (ED), might be compared to finding out that dragons do indeed exist. Or that you could buy temporary invisibility for $10 a pill. Science fiction eminince gris Arthur C. Clarke derived Clarke's Third Law in his book "Profiles of the future: an inquiry into the limits of the possible" (Victor Gollancz/1962): "any sufficiently advanced technology is indistinguishable from magic." And Viagra has turned out to be the technological magic the world had been waiting for (see "The ED Big Three Index").

"I actually think they're underselling Viagra, because it's more than an impotence drug: it's a recreational drug. It eliminates the boundaries between expectation and reality, and permits a level of pleasure that is otherwise just something you hope for. I think it's as important, in its own way, as the birth control pill." 72-year-old Hugh Hefner, as quoted in the 01 April 1999 issue of "Rolling Stone". No surprise, then, that Viagra was found in the stashes of Saddam Hussein's deceased sons, Uday and Qusay.

Viagra is the thought- and marketshare-leader among ED drugs (see "The ED Big Three"), with its main competitors Levitra and Cialis (see "Cialis") fresh on the scene. Uprima, a fourth ED oral medication well-known in Europe and which uses an entirely other biochemical mechanism from the ED Big Three, will probably never be legalized in the U.S. (see "Uprima can't get no respect".) It's worth getting some sense of how Viagra came to be a category-defining drug--as well as a paradigm-smashing cultural phenomenon.

History in the making

Starting in the 1970s, Pfizer had become particularly successful in creating drugs that medicated cardiovascular disease (CVD). Because of the company's good hit-rate with its bestselling CVD drugs, starting in 1985, researchers at Pfizer's Sandwich, Kent (UK) location began looking into new ways to attack CVD, and thus began looking into chemicals that would relax blood vessels in the heart, relieving the pain of angina through increased blood flow. The researchers there made about 1,500 chemicals over the course of four years, among them one with the unremarkable label of UK-92-480, the drug would eventually enable 70+ year-old Hugh Hefner to be bed-hopping with a set of identical twins AND a busty blonde. The category of drugs they were investigating affected nitric oxide (NO) metabolism in the body: NO is a gas that causes blood vessels to relax, and so important is its cardiovascular function that the researchers who discovered this importance won the 1998 Nobel Prize for medicine.

In any event by 1992, Pfizer researchers were finding out that drug code-named UK-92-480 wasn't as helpful for angina as they had hoped; however, by the seventh round of its clinical trials, it became apparent that while healing action on blood pressure and heart muscles wasn't that great, volunteers began to consistently report the same provocative side-effect, which made these very same volunteers not want to give up their use of the experimental drug.

In a case of wonderful scientific synchronicity, academic medical researchers who had nothing to do with Pfizer orcindeed any pharmaceutical company had published studies on the blood-chemistry of erections (see "Science is mankind's brother"). In the late 1980s, UCLA researchers Jacob Rajifer and Louis Ignarro had demonstrated the importance of NO in the erections of rabbits; by 1992, Johns Hopkins University (Baltimore, MD) researchers Arthur Burnett, Charles Lowenstein, David Bredt, Thomas Chang, and Solomon Snyder showed its importance in the erections of dogs and rats.

The Pfizer team headed by Dr. Ian Osterloh, researching what was to become known to all the world as Viagra, suspected there might very well be a link between the happy unexpected side-effect of their rather indifferent experimental angina drug and the newly discovered molecular biology of erections.

In 1993, a dozen British men were the first official human trial subjects for Viagra as ED medication, taking it three times a day for a week, modulating down to once per day. 10 of these plucky volunteers in the phase one trials were -very- satisfied with the results. This dirty dozen comprised the phase one trials for Viagra, and determined its basic pharmacologic and pharmokinetic agency, most common side-effects, and some sense of its dosage.

Phase two trials of the drug, where Viagra's fundamental efficacy was explored, involved men throughout the UK (Royal Victoria Hospital, Belfast, Northern Ireland, was the largest site of these initial drug trials), and in France and Sweden. In these trials, the medicine demonstrated its helpfulness for impotence that is psychogenic in origin.

Researchers in Bristol, England showed erotic videos to volunteers to measure the penile reactions of the then-experimental drug. Viagra by itself does not provoke an erection; external sexual stimulation is also required. If the researchers had not thought through their experimental design thoroughly enough to -include- showing videos to their volunteers, Viagra's power as a remedy for ED would not have been demonstrated.

Phase three, the final testing of the drug, was moved to the United States, where it was demonstrated that Viagra could solve impotence problems that were entirely physiological, such as those caused by diabetes or atherosclerois.

Overall, more than 3,000 men were involved in the clinical trials and commercial development of Viagra; and more than 1,500 Pfizer staffers were involved and more than $400 million was spent. And, at one test site a burglar stole a shipment of the pills, proof for certain of the little blue pills' value.

In 1996, Viagra was given official medical-establishment written imprimateur through articles published in "British Medical Journal" and "Journal of Impotence Research". San Francisco urologist, Dr. Tom Lue, who had directed the phase three studies, delivered the official good news about Viagra at the 1997 meeting of the American Urological Society in New Orleans.

Practical magic had arrived for men. But what about for women? Alas, for women, Viagra is not a magic bullet, or the equivalent of the cloak of invisibility, or the equivalent of -attractive- pantryhose that will never rip.

It's different for girls

While some women have happily experimented with Viagra, and encountered a pleasant augmenting of their sexual repetoire through its recreational use, Viagra doesn't really address the complexity of female sexuality. For example, researchers seeking to understand female sexual arousal have measured pelvic blood flow and clitoral engorgement in women under experimental conditions designed to tease out better understandings of female sexual response. Consistently it's been shown that if female test subjects haven't been given meaningful cognitive or psychological triggers (for example, they've only been shown male-centric erotic videos that don't depict narratives that the women can identify with), the test subjects do not experience themselves as being sexually aroused, regardless what the measurements of their physiology might show. Vasocongestion be damned! As Viagra only acts on local blood flow, and not on the brain, it is of little help to most women, for whom enjoyable sex is a complex mesh of physical and psychological factors.

However, according to Dr. Barbara K. Hogan, sex therapist and assistant professor of psychiatry at Mt. Sinai/New York University Medical Center, Viagra can be of general value to women if the drug is not administered as it is with men--that is, a dose before expected performance--but administered on a daily basis for three to four weeks, which greatly improves pelvic blood circulation overall, which can then lead to enhanced sexual capacity.

The well-known urologist/sexologist Dr. Jennifer Berman had somewhat analogous results when she put women who have had hysterectomies or who are post-menopausal on Viagra: the increase in blood flow improved overall sexual performance and satisfaction for many, although not all, of these women. These are women for whom vascularization of their pelvic regions may have become diminished.

Viagra has also proved helpful for some women who have other circulation-related problems, or who have had spinal cord injuries.

Where Viagra may be of particular help to women is in their efforts to conceive. Because Viagra excels at improving localized blood flow, some infertility specialists have experimented with using Viagra vaginal suppositories with women who have poor endometrial linings. The endometrial lining of the uterus is vascularly rich; causing the smooth muscles (there goes those smooth muscles again!) of the uterus to relax improves both the vascular flow and the supply of estrogen to the endometrium. With a better, thicker, endometrium, women who have experienced either miscarriages or an inability to conceive because their fertilized eggs dont have a rich enough substrate to become implanted in, have been able to successfully conceive a child.

In any event, in 2004 Pfizer finally threw in the towel after eight years of attempts to discover a Viagra for girls. While some women do experience improved sex-lives after having been prescribed testosterone, estrogen, or thyroid, the known female arousal technologies of intimacy, excitement, emotional safety, connection, feeling valued and desireable--these are hard to emulate chemically and put into a jar.

Other uses for Viagra Viagra has begun to be the subject of medical experimentation in non-sexual contexts:

Because of its strengths as smooth-muscle relaxant, Viagra has been shown to helpful in some gastrointestinal conditions. The drug seems to offer some relief of achalasia, a digestive disorder where the valve between the esophagus and the stomach doesn't open regularly; and gastroparesis, a disorder very common among diabetics where the passage of food from the stomach to the intestine is slowed down or blocked.

Returning to its origins as a potential drug for heart conditions, Viagra has helped heart transplant patients who have high blood pressure by lowering that very same high blood pressure. Recall the drug didn't originally seem that helpful for -non- transplant-patients with high blood pressure.

This lowering of blood pressure is linked to another heart-related Viagra good effect. Because Viagra was linked early on to sudden heart attacks and scary drops in blood pressure during sex for men who were taking nitroglycerin for CVD, the drug has been proscribed for men with known heart conditions. However, under certain conditions, sudden drops in blood pressure, and hence, sudden reductions in oxygen flow to the heart, something doctors call preconditioning, can be therapeutic. Preconditioning can protect heart muscle against future injury, reducing the likelihood of death during a heart attack improving the likelihood of a successful outcome of a heart transplant. Experiments have shown that Viagra does precondition hearts--but don't try this at home!

Viagra has also shown particular promise as a treatment for pulmonary hypertension (PHT), the ailment where blood pressure goes berzerk in the arteries feeding the lungs, so that oxygen doesn't get distributed well throughout the body. This is a rare childhood disease, but a common problem among mountain climbers. That is, oxygen-scarce high-altitude air recreates at short notice the nasty breathing problems PHT sufferers have coped with for years. Viagra was taken on a recent Everest expedition to put the PHT-reduction hypothesis to the test; and back in England, Pfizer's Ian Osterloh, the original Viagra head researcher, is conducting phase two trials of his pet drug in the treatment of PHT. Nothing like returning to your roots...

 

Science Is Mankind's Brother

The three main ED drugs all work by inhibiting an enzyme called phosphodiesterase-5 (PDE-5). During sexual stimulation, neurons and endothelial cells lining the arteries of the penis release nitric oxide (NO) into the corpus cavernosum, the spongy erectile part of the organ. NO activates an enzyme called guanylate cyclase, which causes an increase in cyclic guanosine cyclic phosphoric acid (cGMP), a molecule which throughout the body transfers chemical messages from cell surfaces to proteins within cells. cGMP relaxes smooth muscles (smooth muscles line many hollow organs in the body, such as the heart) in the penis; in a flaccid penis, these same muscles are -contracted-. Once blood flows into the corpus structures where it is trapped, two ounces are about all that is needed to create an erection. PDE-5 is also produced at the same time (erections are not supposed to be permanent things!). PDE-5 breaks down cGMP, and hinders the effect of NO. If for either psychological or physiological reasons a man isn't producing enough cGMP, erection problems may result. The Big Three ED drugs work by blocking the cGMP breakdown-effects of PDE-5.

PDE-5 inhibitors had been used by doctors since the mid-1980s to temporarily ease ED, although administered through local injection. The wonder of Viagra and his brothers is that they are taken orally.

Before Viagra and other pills came to dominate the fixing of ED, smooth-muscle relaxants -other than PDE-5 inhibitors- had also somewhat been doing the trick, but were administered in much less aesthetically pleasing ways. The Caverject (marketed by Upjohn, now part of Pfizer) is a one-time-only injection into the penis of alprostadil, which is a synthetic form of prostaglandin E-1; and MUSE (medicated urethral system for erection), marketed by Vivus Inc. (Mountain View, CA.), inserts a lozenge of the same compound into the penis via the urethra. These ED treatment modalities are still around, although have been much supplanted by Viagra.

A collaboration involving a laboratory at a Korean university (department of chemistry, Korea Advanced Institute of Science and Technology, Daejon)), a Korean company (division of drug discovery, CrystalGeonomics Inc., Daejon), and a Japanese university (Protein Design Laboratory, Yokohama City University) led to the unveiling of the 3-D crystalline structures of the Big Three --- sildenafil citrate (Viagra), vardenafil (Levitra), and tadalafil (Cialis) --- each as complexed to erection's foe, PDE-5.

Published as the 4 September 2003 cover story in the prestigious British scientific journal "Nature", the mapping of the combined Big Three/PDE-5 crystalline structures was scientifically significant because it depicted how the drugs actually work pharmacologically.

Crystalline structures of enzymes and proteins, as determined through x-ray diffraction, are not that easily performed, if for no other reason than crystalizing the proteins is not that simple. Perhaps only several thousand proteins have had their crystalline structures identified out of all the millions and quintillions of molecules that exist in the known universe. So it wasn't just salaciousness, but major scientific accomplishment, that led to the Big Three being on the cover of "Nature".

Before the crystalline structures were uncovered, it had been possible to hypothesize how Viagra and his brethren worked: the structures -show- how the compounds fit, lock-and-key style, into the enzyme that breaks, not makes, a viable erection.

There was, of course, major incentive to map out these structures, because once they became known, potential intellectual-property fights aside, it would become much much easier for other corporations to create new (and possiblly better) ED drugs. Knowledge is power! Companies in India and Poland are already set to start manufacturing Viagra under a different brand name, bound to keep international law firms busy for years to come, and Vivus has already started phase two trials of a PDE-5 inhibitor, TA-1790, licensed from Tanabe Seiyaku Co. Ltd. (Osaka, Japan), which seems to be about as effective as Viagra. Maybe it will be cheaper?

To a chemist, it's now easy to see how Levitra and Cialis differ from Viagra and each other.

Levitra, to a chemist, has the look and feel of a classic "me, too" drug. In the pharmaceutical world, the easiest way around a patent is to simply add a methyl molecule (a small, common molecule) to an existing good drug in such a way as to not affect bioactivity. It's rather like coming up with a confection called a brownee, a fudgy chocolatey baked good, and saying 'oh this is quite yummy, it will sate your 4 pm cravings for sugar and chocolate, but no, while it is similar to a brownie, it is not a brownie, it is a brownee.' This looks somewhat the case with Levitra. However Levitra differs from Viagra not only through the addition of a methyl molecule, but also in the re-arrangement of some of its nitrogen atoms. This is a meaningful enough molecular difference as to be likely to cause somewhat different biological activity. Levitra, for example, is said to not cause the unwanted Viagra side-effect of making some fellows see blue, and is said by its manufacturer to last as long as 12 hours, three times longer than Viagra.

Cialis, however, has entirely different structure than Viagra and Levitra, but still fits neatly into the same enzymatic pocket. It is perhaps for this reason that it has different (and some would say, much improved) performance characteristics: it can enable solid erections that can last as long as 48 hours and it doesn't waiver depending on how much and when food was eaten in conjunction with it.

Cialis, to a chemist, looks like a drug likely to have come from a biotech firm, as it did do. Because it is so very different from Viagra and Levitra, it was probably discovered in one of of these two ways: - through a gifted chemist's smart intuition that this molecule might have a sanguine effect on PDE-5; or - through the practice of running 40 million hundred zillion potential molecules through computer chemical-simulation programs, with the hope that one will have the same performance characteristics and biological fit as a hit medicine. The theory is that computational chemistry can discover a medicine that works the same as a hit medicine, even if the novel medicine's structure is entirely different from that of the hit medicine.

While the commericial development and testing of Cialis lagged a few years behind Viagra, doctors had known since the mid-1980s that relaxing penile smooth muscles was a way to create erections. Given that ICOS researchers went to work about the time the very first trials of Viagra - as an ED remedy - were being undertaken, it's probably the case that the Washington state researchers saw that PDE-5 inhibitors -in general- were a swell way to go about creating an ED drug of their own, and not that they were trying to overtly knock off Viagra.

 

Outline of Contents

Viagra Chapter:
The ED Big Three
The ED Big Three Index
Animal Brothers
Science is Mankind’s Brother
Uprima
Cialis
The 6000 Names of a Minor Diety

First Persons:
Dennis Waskul
Craig Newmark
Elena Dorfman
Natacha Merritt
Paul Festa
Eric Janssen

Image Archive

The ED Big Three

  • Viagra (sildenafil citrate) brought to you by Pfizer Inc. (New York, NY).
    FDA approved 1998.
  • Levitra (vardenafil) manufactured by Bayer AG (Leverkusen, Germany), the
    same folks that brought you aspirin and in World War II, the industrial combine I.G.Farben. Levitra is co-marketed with British Big Pharm multinational GlaxoSmithKline (Middlesex, UK). FDA approved autumn 2003.
  • Cialis (tadalafil) arrived throught a joint venture (Lilly ICOS) between
    old-time U.S. drugmaker Eli Lilly and Company (Indianopolis, IN) and ICOS Corp (Bothell, WA). FDA approved autumn 2003.

 

 

The ED Big Three Index

  • minimum amount of time it can take for Viagra to work, on an empty stomach: 20 minutes
  • minimum amount of time it can take for Levitra to work on an empty stomach: 16
  • minutes optimal amount of time for Viagra to work, on an empty stomach: 60
  • minutes maximum time Viagra can work: 4 hours
  • number of prescriptions written for Viagra since its introduction: 130 million number of men worldwide who have tried Viagra: 20
  • million number of Viagra pills dispensed worldwide every second: 9
  • number of doses per month U.S. veterans receving VA pharmacy benefits are allowed: 4
  • refill rate, in percentages, of Viagra prescriptions in the U.S.: 50 refill rate, in percentages, of Viagra prescriptions in the U.K.: 75
  • decline, in percent, of new monthly prescriptions written for Viagra in the UK during the World Cup soccer playoffs in 2002: 50
  • increase, in percent, of new prescriptions written for ED drugs in the two weeks after the U.S. 2004 Superbowl, with its televised advertisements for all three of the ED Big Three: 16
  • ranking of Viagra of drugs bought in the U.S. from online pharmacies: 2
  • percentage of Viagra prescriptions filled for men under the age of 40: 8 (Ashton Kutcher gives a thumb's up)
  • amount in pounds of Viagra manufactured weekly in Ringaskiddy, Cork County, Ireland, and shipped in 55-pound drums to Pfizer plants in France, Puerto Rico, and the U.S.: 3,080
  • number of erections per 55-pound drum: 5,000
  • percentage of men in double-blind tests who found Viagra effective for ED: 75 percentage of men in double-blind tests who found a blue sugar pill effective for ED: 25
  • percentage of men, according to Viagra manufacturer Pfizer, who prefer Cialis to Viagra: 21
  • percentage of men, according to Cialis manufacturer Lilly ICOS, who prefer Cialis to Viagra: 73
  • percentage of men taking Cialis who wait 12 hours after taking the medication before having sex: 50
  • Viagra profits for Pfizer by 2002: $6 billion
  • Worldwide sales of Viagra in 2002: $1.74 billion
  • U.S. sales of Viagra in 2002: $1 billion
  • amount earned in one year by the Church of England through its timely investment in Pfizer, through the Viagra-caused doubling of the company's stock price: $3.3 million
  • fine levied, in U.S. dollars, on a Brazilian legislator who attempted to buy votes with Viagra for a seat in his country's lower house of congress: $7,240
  • additional time, in days, that researchers in Israel and Australia found that adding 1/50th of a dose of Viagra to water will keep cut flowers and harvested vegetables fresh: 7
  • percentage of men who observe a blue haze after taking Viagra, because the enzymes in their retinas respond peculiarly to the drug: 3
  • number of hours the FAA requires pilots to wait between taking Viagra and flying, because of the possibility of their seeing blue: 6
  • U.S. patent number for a Viagra-based chewing gum filed by the William Wrigley Junior Co. (Chicago, Ill): 6,531,114
  • number of partners Viagra-users enlisting the services of a San Francisco STD clinic had entertained in the previous two months: 5.4
  • number of partners non-Viagra users showing up at the same San Francisco STD clinic had entertained during the same time period: 3.5
  • ratio of gay men receiving a diagnosis of syphilis after having used both methamphetamine and Viagra in the previous four weeks, relative to gay men receiving a diagnosis of syphilis who have used neither drug in the previous four weeks: 6:1
  • ratio of gay men engaged in an act of unprotected insertive anal sex, who took Viagra, relative to gay men engaged in an act of unprotected insertive anal sex, who had not taken Viagra: 6:1
  • Year Pfizer loses the patent on Viagra, and generic Viagra becomes legal instead of being a scary Internet spam scam: 2013
  • overall percentage of men with ED for whom Viagra will work, if proper counseling and instruction is provided: 80
  • percentage of men with ED and vascular disease for whom Viagra will work: 65
  • percentage of men with ED and complicated medical conditions for whom Viagra will work: 50
  • percentage of men with ED caused by radiation treatment for prostate cancer, for whom Viagra will work: 75
  • percentage of men with ED caused by surgery for prostatic cancer, who have had both prostatic nerves saved, for whom Viagra will work: 45
  • percentage of men with ED caused by surgery for prostatic cancer, who have had only one prostatic nerve saved, for whom Viagra will work: 25

Uprima: Just Can't Get No Respect

In the early 1990s, while Viagra was mostly still a twinkle in drug-maker Pfizer's eye, three researchers at Queen's University (Kingston, Ontario, Canada) went looking to develop a Canadian ED drug. Doctors Jeremy Heaton, Michael Adams, and Alvara Morales, along with a Chicago-based researcher named Ragab el Rashidy, homed in on Uprima, chemical name apomorphine, a compound that had been used to treat Parkinson's disease and to induce vomiting in drug-overdose patients.

Before the advent of Uprima, apomorphine has somewhat gone out of fashion in the medical community. There are newer better treatments for Parkinson's, and emetics have almost entirely gone out of use in emergency medicine. Apomorphine -was- used at one time in the attempt to decondition alcholics (under a doctor's supervision, take a shot of bourbon, get a shot of apomorphine, and enjoy the violent vomiting that ensues...are you sure you want that second drink?).

What led to apomorphine's off-label revival as a ED drug stems from observations Montreal scientists had made in the 1970s about dopamine's salutary effects on the behavior of erectile tissue in the penis. Uprima aka apomorphine is a dopamine-receptor agonist (dopamine metabolism is affected in Parkinson's, hence the drug's therapeutic use there), meaning it targets and enhances the pathways and receptors in the brain that release and are sensitive to dopamine. Uprima's mechanism of causing erections therefore differs from that involved in the Big Three ED drugs, which operate in localized fashion on the blood-chemicals in the penis that control erections.

In fancy neurological terms, Uprima reduces inhibatory signalling and increasing positive signalling. By increasing production of dopamine, particularly in the portion of the brain called the hypothalamus (which mediates all kinds of normal human drives), Uprima sends better stronger signals down the spinal cord into the genitals of ED sufferers, leading to hoped-for erections. It's another case of mind over matter!

Interestingly, there is some evidence to suggest that Uprima may work far better for women than Viagra seems to. A Scottish study of women going through menopause found that women given increasingly higher doses of the drug reported increases in arousal, desire, and overall sexual satisfaction.

One theory about why Uprima seems to work better for women than Viagra is that the limbic system, the part of the brain tied to emotional responses, is packed with dopamine receptors. Female sexual response is far more tied to cognitive and emotional cues than male sexual response; increases in genital blood flow by themselves will not, in women as it usually does in men, lead to a reported subjective sense of increased desire and arousal. Because Uprima's acts in the central nervous system, and not on localized blood flow, making it a better fit with how women actually function as sexual beings.

Available in 50 countries since 2000, Uprima is administered under the tongue, in part to limit potential gastrointestinal side-effects (nausea and sex made strange bedfellows). It takes effect in 17 minutes, and will work for patients who have CVD, which would contraindicate use of the ED Big Three.

However, Uprima may never become legal in the U.S.: TAP, a joint venture of U.S. pharmaceutical giant Abbott Laboratories (Abbott Park, Ill) and the Japanese company Takeda Industries (Tokyo, Japan), withdrew its new-drug application for Uprima from the FDA because of the drug's unfortunate tendency to cause fainting in some individuals. When the FDA learned that one test subject fainted in his doctor's office and cracked his skull after taking the drug and another, in -his- Uprima-induced faint, cracked his car up, TAP made the decision that discretion is the better part of valor, and decided not to attempt to legalize the drug in the U.S.

 

Cialis, The Little -Yellow- Pill

In the nine months after it appeared on the market in Europe and Australia in 2003, Cialis snapped up 30 percent of the ED market, such that 1 million men had tried it: 18 percent of the ED prescriptions in Spain and in the UK, and 30 percent in Germany. In fact, in Italy and France, new prescriptions for ED by primary-care physicians are now being written more often for Cialis than for Viagra.

By the end of 2003, Cialis had given rise to $203 million in sales worldwide, and a nickname, "le weekend", reflective of the drug's efficacy of about 36 hours. Like Levitra, the drug became legal in the U.S in November 2003 --- and within two months had gained almost five percent of the U.S. ED prescription market.

Cialis is marketed by Lilly ICOS, a joint venture between ICOS, a Puget Sound company, and Eli Lilly, the pharmaceutical giant. It is manufactured in Lilly's Puerto Rican factory. After 10 years and hundreds of millions of dollars in development costs (typical for any new drug which can meet the requisite regulatory and scientific challenges), Cialis became the first marketable drug ICOS developed. Research began on IC351 (what became Cialis) in 1993, with a patent being granted in 1994. First clinical trials began in 1995.

ICOS is a 14-year-old biotech startup which has had a higher than average rate of failure for the drugs in general it has attempted to develop. In 2002 it had eight experimental drugs it was testing; by 2004, it had only one under development. Microsoft's Bill Gates owns 13 percent of the company (it's good to diversify!)

Cialis has also acquired an interesting Eastern European spokesmodel. Janis Naglis, a former mechanical engineer and former head of the Latvian Privatization Agency, is chairman of the ruling Latvia's Way political party and has been voted by Latvian women's magazines as one of the most attractive men in Latvia.He is also -the- Latvian celebrity endorser of Cialis. This makes him unique in the world, because he is the only celebrity endorser of Cialis. Lily ICOS, in a departure from the celebrity endorsement tactics of Levitra manufacturer Glaxo Smith Kline/Bayer (using, for example, former star football coach Mike Ditka) and Viagra manufacturer Pfizer (using, for example, former senator Bob Dole, former soccer superstar Pele, former hockey superstar Guy Lafleur, former Texas Rangers MVP Rafael Palmeiro, current NASCAR driver Mark Martin) has a marketing campaign that explicitly avoids celebrities and instead emphasizes intimacy, relaxation, and connection between ordinary people.

Strangely, Cialis has been illegally remarketed as a dietary supplement sold over the counter to improve general alertness and stamina.

Folks with the surname Cialis in Canada and the UK are considering suing ICOS. No such lawsuits seem to be pending for people with surnames Viagra and Levitra.

 

 

The 6,000 Names of a Minor Deity

An assortment of ways spammers spell and misspell "Viagra", as harvested between August 2003 and April 2004. After all, according to "Library Journal", (and librarians -do- know everything), "Viagra" was the most common subject line in spam in 2003:

viagra, viagraa, v1agra, wiaggra, v_i_a_g_r_a, v.i.a.g.r.a, v*i*a*g*r*a,
v-iagra. blue pill; blu pill; little blue pill, viagr@, vi agra, blue passion, viag%ra, v^i^a^g^r^a, v/agra, /=v=i=a=g=r=a, v1agro, tiny blue pill, v-1agra, v...i^g"*r+a..., viag%ra, v < i < a > g < r > a, via -- gra, v!agra, /...v - iagra/, v.i.a^g.r.a, v'iag>ra, vi)agra, vi..ag..ra.., viag#a, via.gra, V':I'A'G'R'A, via=gra, vriagra, vi@gr@, v1agr1a, v-iag*ra v1agro, v1@gra v^i_a_g_r_a.., v**i*a**g*r**a, V_I,A.G,R.A, V_I.A.G.R_A, via!gra, v&iagra, v(iagra!!, via!gra, v&iagra, viagmra, v.1agr.a, via-gra, v[phi]agra, vi -agra, v^iagra, viabGra, vagrgra, viakgra, ZViaqra, VU1aqGra, VWiagrCa, PViaqrah, Va1aqFra, VaiagrFa, 1ViaqraI, viagram, viagrac, viagrOa, viagr2a, ViagTra, viagrua, viagMra, viagrFa, viagrBra, viagRdra, viagrXFra, vIrGRA, Viagr, viagrbxa, viagjara, viagykra, ViagOAra, v:gRa, viagrMMa, v:@gra, ViagVrNa, viagztra, viahrWga, v *i * a *g *r *a * * *, vigra s, vlaGR@, vaigra, Via agra, v-ii-a=g-ra, VFiagra, v!agra!, vi**agra!, v*i-a-g.r-a, vi@gr*@, v*i-a-g-r-a, ViagrTEA, ViagrJba, Vi"agra, Viag#rHa, V.@GRa, viagdra, vi@gRa, v:agR@, viagr&a, v;iagra

 

 

Animal Brothers

One of the more intriguing, if somewhat controversial, consequences of Viagra's speedy rise to global drug superstardom are its links to the animal kingdom. There is some evidence to suggest that the drug, because it is an anti-impotence medication that works on blood chemistry and not on faith, has diminished trafficking in parts of animals used as aphrodisiacs in folk and traditional medicines, particularly in Asia.

Conservation biologist Frank von Hippel at the University of Alaska, along with his brother William von Hippel, psychology professor at the University of South Wales, Australia, made a stir in 2002 thorugh their study suggesting that Viagra has had some place in the reduction of sales of animal parts.

For example, sales of Alaskan reindeer velvet, a traditional Chinese medicine (TCM) thought to enhance potency, declined by 72 percent from 1997 to 1998, a decline much greater than the decline in sales of reindeer meat during the same period. Young Yoon, proprietor of the Oriental Shopping Center (Anchorage, AK), was forced to drop the price of his pre-packaged sliced deer horn by 50 percent between 1997 and 2002; U.S. sales of the TCM powered red medicine Strong Man at a Philadelphia TCM apothecary also have not been what they once were.

The sex organs of Canadian harp and hooded seals, long a fine would-be potency-enhancing export item to Asian markets, fell in price from approximately $100 a pop to about $15 between 1998 and 2000. By 2002, there were rumors of freezers full of unsold seal private parts (is freezer burn an issue here?).

And, in an informal survey the von Hippel brothers made of Hong Kong apothecaries, it appeared that prices for TCM virility cures had come down, suggesting that these medicines now had some serious competition from the West. Sales of Viagra immediately jumped 10 percent after travel restrictions for mainland Chinese residents were lifted, allowing them to have easy access to Hong Kong and its more Westernized markets. Because 90 percent of the Viagra in mainland China is fake, and a prescription is only available after a hospital visit, it's not surprising that Viagra may not yet have had the impact environmentalists and animal lovers would like to have had the harvesting of everything from sea-horses to black rhinocerii.

Whether Viagra will truly have an impact on endangered species will always be hard to determine, because trafficking in such critters is illegal internationally, so there are no official statistics kept.

That being said, Viagra has been used in direct -support- of endangered species. Viagra has been given to the fewer than 30 remaining South China tigers, in the hopes of improving their reproductive capacities. It has also been given to Giant Pandas for the same reasons: in both cases, captive males of these endangered species were not exhibiting sufficient sexual desire to foster baby-making.

But pity the poor grayhounds that course in Irish races: they are prohibited from taking Viagra, on the rumored chance that it, like steroids, may give them an unfair advantage at the track.