Posts tagged drugs
Articles and news from the latest research reports.
Seeking new methods to treat heroin addiction
“Heroin itself is an inactive substance,” explains Jørg Mørland, Norwegian forensic medicine and toxicology researcher. “The substances that heroin forms in the body are mainly what enter the brain and cause the narcotic effects.”
The heroin high and feelings of pain relief manifest themselves almost immediately after the drug has been injected. Yet it was shown many years ago that heroin is inactive at the opioid receptors in the brain.
So what is it about heroin that brings about such a pronounced effect? A number of research projects funded under the Programme on Alcohol and Drug Research (RUSMIDDEL) at the Research Council of Norway may help to solve the mystery.
“Gaining a thorough understanding of the effects of heroin and of the neurobiological mechanisms involved will be a valuable basis for the development of new treatments for addiction,” states Jørg Mørland, who is the project manager of an ongoing project on this important subject, the most recent in a long line of such Norwegian projects which he has headed.
Dr Mørland is a senior researcher at the Norwegian Institute of Public Health and Professor emeritus at the University of Oslo. Through studies on rats and mice, he and his colleagues have come up with new findings that may be significant to the development of new treatment methods.
Heroin metabolises rapidly
One widely-held theory has been that heroin passes quickly into the brain where it is converted into morphine, and that what users are actually experiencing are the effects of morphine. As it turns out, however, heroin undergoes a number of important transformations on its way to the brain. Just a few minutes after injection, the conversion of heroin into the metabolite 6-MAM is almost complete.
“Our research shows that it is primarily 6-MAM that crosses the blood-brain barrier and that heroin as such only enters the brain to a small degree. Thirty minutes after injecting heroin, 6-MAM is the predominant substance both in the blood and in the brain,” Dr Mørland explains.
The presence of 6-MAM also results in a sharp increase in the signalling molecule, dopamine, in certain areas of the brain. This plays a pivotal role in the rewarding effect.
“This points towards 6-MAM as the main substance behind all the acute effects of heroin,” says Dr Mørland.
“After about an hour, most of the 6-MAM has been converted into morphine. Morphine acts rapidly on the body and is the dominant component for the next hours, but from six to twelve hours after injection the effects observed are mostly consequences of a metabolite formed from morphine, morphin-6-glucuronide.
Looking for a new treatment
“We are working to understand the roles of all these metabolites and to investigate potential treatments to counter their effects,” Dr Mørland states.
The current approach to treating heroin addiction in Norway is pharmacotherapy – using methadone, subutex or subuxone. These are synthetic substances that all work in the same way as heroin, however, and are addictive in their own right.
“The treatment method involves administering these substances over the course of a day to reduce the rewarding effect. The intent is to diminish the patient’s preoccupation with finding heroin in order to lead a more normal life,” Dr Mørland points out.
Researchers at the Norwegian Centre for Addiction Research (SERAF) in Oslo are examining sustained-release naltrexone – a non-addictive opioid antagonist that blocks the effects of opiates in the brain. Dr Mørland is hopeful that his research will make it possible to affect opiates even before they reach the brain.
An opiate roadblock
“It may be possible to block these substances from ever entering the brain, thereby modifying the effect of heroin,” Dr Mørland adds.
As part of a new project, he and his colleagues will study the effect of a 6-MAM antibody developed by a Norwegian company. The antibody binds to the 6-MAM in the blood, making the 6-MAM molecule too large to cross the blood-brain barrier.
“If we succeed in getting this antibody to work it could block much – and maybe even all – of the effect of heroin,” the researcher concludes.
Can Blood Pressure Drugs Reduce the Risk of Dementia?
People taking the blood pressure drugs called beta blockers may be less likely to have changes in the brain that can be signs of Alzheimer’s disease and other types of dementia, according to a study released today that will be presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego, March 16 to 23, 2013. The study involved 774 elderly Japanese-American men who took part in the Honolulu-Asia Aging Study. Autopsies were performed on the men after their death. Of the 774 men, 610 had high blood pressure or were being treated with medication for high blood pressure. Among those who had been treated (about 350), 15 percent received only a beta blocker medication, 18 percent received a beta blocker plus one or more other medications, and the rest of the participants received other blood pressure drugs.
The study found that all types of blood pressure treatments were clearly better than no treatment. However, men who had received beta blockers as their only blood pressure medication had fewer abnormalities in their brains compared to those who had not been treated for their hypertension, or who had received other blood pressure medications. The brains of participants who had received beta blockers plus other medications showed an intermediate reduction in numbers of brain abnormalities.
These included two distinct types of brain lesion: those indicating Alzheimer’s disease, and lesions called microinfarcts, usually attributed to tiny, multiple, unrecognized strokes. Study participants who had taken beta blockers alone or in combination with another blood pressure medication had significantly less shrinkage in their brains.
“With the number of people with Alzheimer’s disease expected to grow significantly as our population ages, it is increasingly important to identify factors that could delay or prevent the disease,” said study author Lon White, MD, of the Pacific Health Research and Education Institute in Honolulu. “These results are exciting, especially since beta blockers are a common treatment for high blood pressure.”
Earlier research has shown that high blood pressure in midlife is a strong risk factor for dementia.
Bryan Saunders, a performance and visual artist, undertook a high profile experiment in creativity, starting several years ago whereby, according to the artist, he created a series of self-portraits, each one done under the influence of a different substance—pretty much an A to Z assortment, from prescription meds like Abilify and Xanax to crystal meth. Over the weeks he’d create amazing pieces, suffer mild brain damage and end up hospitalized—all for the sake of art and creation.
Prospective Alzheimer’s drug builds new brain cell connections
Washington State University researchers have developed a new drug candidate that dramatically improves the cognitive function of rats with Alzheimer’s-like mental impairment.
Their compound, which is intended to repair brain damage that has already occurred, is a significant departure from current Alzheimer’s treatments, which either slow the process of cell death or inhibit cholinesterase, an enzyme believed to break down a key neurotransmitter involved in learning and memory development.
Such drugs, says Joe Harding, a professor in WSU’s College of Veterinary Medicine, are not designed to restore lost brain function, which can be done by rebuilding connections between nerve cells.
"This is about recovering function,” he says. "That’s what makes these things totally unique. They’re not designed necessarily to stop anything. They’re designed to fix what’s broken. As far as we can see, they work.”
Harding, College of Arts and Sciences Professor Jay Wright and other WSU colleagues report their findings in the online “Fast Forward” section of the Journal of Pharmacology and Experimental Therapeutics.
(Source: news.wsu.edu)
Epilepsy in poor regions of the world
Epilepsy is a common disorder, particularly in poor areas of the world, and can have a devastating effect on people with the disorder and their families. The burden of epilepsy in low-income countries is more than twice that found in high-income countries, probably because the incidence of risk factors is higher. Many of these risk factors can be prevented with inexpensive interventions, but there are only a few studies that have assessed the effect of reducing risk factors on the burden of epilepsy. The mortality associated with epilepsy in low-income countries is substantially higher than in less impoverished countries and most deaths seem to be related to untreated epilepsy (eg, as a result of falls or status epilepticus), but the risk factors for death have not been adequately examined. Epilepsy is associated with substantial stigma in low-income countries, which acts as a barrier to patients accessing biomedical treatment and becoming integrated within society. Seizures can be controlled by inexpensive antiepileptic drugs, but the supply and quality of these drugs can be erratic in poor areas. The treatment gap for epilepsy is high (>60%) in deprived areas, but this could be reduced with low-cost interventions. The substantial burden of epilepsy in poor regions of the world can be reduced by preventing the risk factors, reducing stigma, improving access to biomedical diagnosis and treatment, and ensuring that there is a continuous supply of good quality antiepileptic drugs.
Kansas State University researchers have discovered a molecule that may be capable of delivering drugs inside the body to treat diseases.
For the first time, researchers have designed and created a membrane-bounded vesicle formed entirely of peptides — molecules made up of amino acids, the building blocks of protein. The membrane could serve as a new drug delivery system to safely treat cancer and neurodegenerative diseases.
A study led by John Tomich, professor of biochemistry at Kansas State University, has been published in the journal PLOS ONE in September, and a patent for the discovery is pending.
(Source: k-state.edu)
Pill Found Promising in Treatment of M.S.
A new oral medication to treat patients in the early stages of has shown considerable promise in two clinical trials, researchers announced on Wednesday.
The medication is on track to become just the third oral drug available to M.S. patients, and potentially the safest and most effective, experts said. The second oral drug, called Aubagio, was approved just last week.
M.S. was virtually untreatable only two decades ago, but today nine “disease modifying” drugs are available for early-stage patients; a half-dozen more are in the late stages of development. Most patients in the early stage of the disease, a form called relapsing-remitting M.S., take drugs by injection.
The two new studies, published online in The New England Journal of Medicine, found that the drug BG-12, developed by Biogen Idec, reduced relapse rates in patients with relapsing M.S. by about 50 percent. The drug also significantly reduced the frequency of new brain lesions often associated with these attacks, and slowed the progression of disease compared with a placebo.
The studies were Phase 3 trials, a last step on the road to drug approval. The Food and Drug Administration is required to make a decision about the drug’s approval before the end of this year.
“This drug is clearly quite effective in managing disease and reducing disability, and the safety profile looks quite good,” said Timothy Coetzee, the chief research officer at the National Multiple Sclerosis Society, who was not involved in the studies.
is often a progressive disease in which the immune system damages neurons in the brain and spinal cord. A majority of people with M.S. have relapsing-remitting M.S., characterized by flare-ups that cause lesions in the brain to develop and neurological symptoms to emerge or worsen. Eventually, more than half of patients develop a progressive form of M.S., leading to permanent disabilities.
Interferons, the drugs most commonly used in relapsing M.S., reduce relapses by about 30 percent, and have not been shown to slow the progression of the disease and disability. The newly approved Aubagio also reduces relapses by about 30 percent, and it has the advantage of being an oral drug.
Two drugs that are substantially more effective, and Gilenya, come with serious risks including, in rare cases, death. They are used as second-line treatments when an initial approach fails, and patients require some monitoring.
In the new studies, called Define and Confirm, patients were randomized into two groups, taking 240 milligrams of BG-12 either twice or three times a day. Patients in a third group took a placebo. The combined results showed that the drug reduced the relapse rate by about 50 percent. There was minimal difference between the twice-daily and thrice-daily regimens.
Taking BG-12 twice a day reduced the number of new or newly enlarging brain lesions by 71 percent to 99 percent, depending on the type of lesion and the study. The Define study found a statistically significant 38 percent reduction in the progression to disability.
The most frequent side effects were a temporary flushing and warm feeling and gastrointestinal symptoms including nausea, , cramping and . Though both types of side effects were common, they tended to diminish after the first few weeks of use and were tolerated by most patients.
BG-12 is an anti-inflammatory that works by protecting nerves against injury. It is a fumaric acid, very similar to one widely used in Germany for the treatment of . “The safety track record is well known and appears to be very strong,” said Dr. Robert Fox, lead author of one of the two new studies and medical director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.
“It’s a bright day for M.S. patients, but there is a gray cloud in that we still don’t have anything for those with progressive M.S.,” he added.
The mechanism of action of cocaine
Cocaine modifies the action of dopamine in the brain. The dopamine rich areas of the brain are the ventral tegmental area, the nucleus accumbens and the caudate nucleus – these areas are collectively known as the brain’s ‘reward pathway’. Cocaine binds to dopamine re-uptake transporters on the pre-synaptic membranes of dopaminergic neurones. This binding inhibits the removal of dopamine from the synaptic cleft and its subsequent degradation by monoamine oxidase in the nerve terminal. Dopamine remains in the synaptic cleft and is free to bind to its receptors on the post synaptic membrane, producing further nerve impulses. This increased activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with cocaine use.
Building a human on a chip, organ by organ
Human “organs on chips” could be linked to make the ideal guinea pig, revolutionising the way drugs are tested and cancer is treated
Such organs on chips can be used to model how human organs function and respond to drugs, says Ingber. He thinks that they even have the potential to eliminate the use of animals in drug testing. “Animal testing is expensive and time-consuming, and animals are not always representative of humans.”
Still, Ingber points out that the chips can perform some roles that animal studies cannot. For instance, they could be personalised by building them from an individual’s own cells. In theory, a doctor could send tissue samples to a lab to test a potentially harmful therapy on such a chip before handing out a prescription. This would be especially useful for people with cancer, as the various therapies available can have very different effects on different people, Ingber says. “You could get a quick yes-or-no answer to whether a drug would work or not,” he says.
Personalised chips might also speed up clinical trials. “Someday it might be possible to shortcut clinical trials by using chips containing cells from different human populations that are known to respond differently to specific drug classes,” Ingber says.
Statin Use Appears Associated with Modest Reduction in Parkinson Disease Risk
March 12th, 2012
Regular use of cholesterol-lowering statin drugs may be associated with a modest reduction in risk for developing Parkinson disease, particularly among younger patients, according to a study in the March issue of Archives of Neurology, one of the JAMA Archives journals.
Statins are one of the most prescribed classes of drugs in the United States and some researchers have hypothesized that the anti-inflammatory and immunomodulating effects of these medications may be neuroprotective. However, statins also may have unfavorable effects on lowering the level of plasma coenzyme Q10, which may be neuroprotective in patients with Parkinson disease (PD), the researchers write in their study background.
Xiang Gao, M.D., Ph.D., of Brigham and Women’s Hospital and Harvard School of Public Health, Boston, and colleagues conducted a prospective study that included 38,192 men and 90,874 women participating in the Health Professional Follow-up study and the Nurses’ Health study.
During 12 years of follow-up from 1994 to 2006, researchers documented 644 incident PD cases (338 in women and 306 in men).
“In summary, we observed an association between regular use of statins and lower risk of developing PD, particularly among younger patients,” the researchers comment. “However, our results should be interpreted with caution because only approximately 70 percent of users of cholesterol-lowering drugs at baseline were actual statin users. Further, the results were only marginally significant and could be due to chance.”
Researchers note that because they classified the use of any cholesterol-lowering drugs before 2000 as statin use, misclassification was inevitably introduced. They also did not collect information on the use of specific statins, which could have different effects on the central nervous system.
When researchers did observe a significant interaction between statin use and age in relation to PD risk it was among study participants younger than 60 years at the start of follow-up, not among those participants who were older.
The authors note that not only have epidemiologic studies produced mixed results on statin use and PD risk, but statins also may have unfavorable effects on the central nervous system.
“In contrast with use of ibuprofen, which has been consistently found to be inversely associated with PD risk in these cohorts as well as in other longitudinal studies, the overall epidemiological evidence relating stain use to PD risk remains unconvincing,” the authors conclude. “Given the potential adverse effects of statins, further prospective observational studies are needed to explore the potential effects of different subtypes of statin on risk of PD and other neurodegenerative diseases.”
(Arch Neurol. 2012;69[3]:380-384).
Source: Neuroscience News