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  • Vaccine saved rats from opiate overdose

    American scientists have tested a conjugate vaccine on rats that protects against an overdose of the opioid drug fentanyl. In vaccinated animals, which were injected with toxic doses of the substance, its concentration in the brain was ten times lower than in unvaccinated ones. However, the drug turned out to be narrowly targeted: it protected animals only from two types of opiates - fentanyl and sufentanil. The study was published in the journal Pharmaceuticals.

    Addiction to opiates - morphine, heroin, codeine and their derivatives - continues to be a serious problem throughout the world. Moreover, in some countries, the use of artisanal and illegal opiates dominates, while in others, the use of medications (for example, the opioid crisis in the United States).

    There are various strategies to reduce the harm to human health and society from opiates. The use of opioid receptor antagonists interferes with the enjoyment of drug use, preventing addiction from forming and reducing the risk of overdose. But patients are quite difficult to tolerate these drugs.

    For those who cannot be forced to abstain from opiates, there is long-acting drug replacement therapy. But such treatment does not fully protect against overdose and is prohibited by law in a number of countries. Exotic means to relieve withdrawal symptoms (we talked about one of these) have not yet become widespread. In any case, effective addiction treatment must be long-term and continuous.

    Back in the second half of the last century, scientists tried to create vaccines against addictive substances. This list includes opiates, nicotine, methamphetamine and cocaine. The antibodies that should arise in a vaccinated person should intercept the drug in the blood, preventing it from entering the brain. Accordingly, taking the drug will not cause a feeling of euphoria.

    But due to the small size of the molecules, the immune system does not recognize opiates well. As a result, even the results of animal experiments were rather modest: either the formulas used were unsuitable for use in humans, or they did not work even in experimental animals. As a result, previous generations of vaccines were ineffective.

    Pharmacologists and narcologists from the Universities of Houston and New Orleans, with the participation of Colin N. Haile, tried to create a vaccine against fentanyl, a powerful opioid analgesic that has become widespread in several countries as a drug.

    In their conjugate vaccine, the drug was linked to an immunogenic protein derived from diphtheria toxin. To enhance the immune response, they added an enterotoxin-based protein adjuvant to the mixture. To test the effect on animals, 16 males and females were taken (female rats are several times less sensitive to opiates).

    The triple vaccination protected the animals from the effects of the drug: after administration of fentanyl (at a dose of about 10 percent of the semi-lethal dose), the vaccinated animals had the same pain sensitivity and efficiency in performing cognitive tasks as if they had not been given the drug. Vaccination prevented bradycardia and reduced blood oxygen levels, the physiological changes that occur with opiate overdose. The concentration of fentanyl in the brain of vaccinated animals was ten times lower than that of unvaccinated animals.

    Testing for cross-reactivity of antibodies showed that fentanyl vaccination also helps against its derivative, sufentanil. But it was ineffective against compounds with a different chemical structure - morphine, methadone, buprenorphine and oxycodone.

    It is not yet clear how persistent such immunity is - scientists tracked the effect of the vaccine only within 10 weeks from the first immunization. The use of highly immunogenic conjugates made it possible to obtain a high level of antibodies to the drug and revive the idea of a vaccine against opiates. If the method comes to be used in humans, then such treatment should combine the advantages of opioid receptor antagonists and good tolerability. True, a wide range of chemical structures of opiates will not allow creating a single monovaccine against all opiates. But this should not be a serious problem, because combined conjugate vaccines can include dozens of haptens.

    Author DeepWeb
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