Vaccines against drugs of abuse: where are we now?

Kinsey, Berma M.

doi:10.1177/2051013614537818

Cited by 32 publications

(29 citation statements)

References 96 publications

(148 reference statements)

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“…A large body of literature supports the overall concept of vaccination for the treatment of drug abuse, where a small molecule hapten-protein conjugate is delivered with the intention of generating antibodies that sequester the target drug in the periphery, preventing induction of central nervous system (CNS) mediated effects. 21 A ‘dynamic’ variant of this general approach was recently developed to blunt heroin self-administration, wherein a single chemically-labile hapten was used to induce antibodies directed against multiple opioid metabolites. 22 These foundational studies inspired us to pursue a generalizable ‘dissection through vaccination’ method that could isolate the effects of single compounds within a structurally- and pharmacologically-diverse chemical system, such as that generated by fenethylline.…”

Section: Mainmentioning

confidence: 99%

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Wenthur

Zhou

Janda

2017

Nature

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SUMMARY PARAGRAPH Fenethylline, also known as Captagon, is a synthetic psychoactive stimulant that has recently been linked to substance use disorder and ‘pharmacoterrorism’ in the Middle East.1–4 Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it additionally incorporates a covalently-linked xanthine moiety into its parent structure.5,6 These independently-active pharmacophores are liberated during metabolism, resulting in a structurally-diverse chemical mixture being deployed to the central nervous system.7–9 Although fenethylline’s psychoactive properties have been reported to differ from other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects.10,11 Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate fenethylline’s psychoactivity and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacologic activity. We anticipate that DISSECTIV will be employed to expose unidentified active chemical species and illuminate pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples, and natural product extracts.

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Section: Mainmentioning

confidence: 99%

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Wenthur

Zhou

Janda

2017

Nature

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“…İlk nikotin aşısı da 1973 yılında denenmiştir. İki binli yıllarda da ilaç endüstrisi nikotin aşıları ile ilgili klinik çalışmalara başlamıştır (45,46) . İlk yıllarda çalışılan aşılarda bakteri ve virüs toksinleri gibi taşıyıcı proteinler kullanıl-mıştır.…”

Section: Immunoterapi (Nikotin Aşısı)unclassified

“…Multivalan aşılarla ilgili henüz hiç klinik çalışma yoktur (46) . Nikotin aşıları ile yapılan deneysel çalışmalarda nikotinin beyne geçişinin azaldığı ve yarı ömrünün de uzadığı gösterilmiş olmakla birlikte nikotinin beyne ulaşması tamamen engellenememiş ve klinik çalış-malarda deneysel çalışmalarda elde edilen yüz gül-dürücü sonuçlar alınamamış, nikotin aşılarının uzun süreli sigara bırakmadaki etkisi de zayıf bulunmuş-tur (45,46) . Bunun pek çok nedeni olabilir.…”

Section: Immunoterapi (Nikotin Aşısı)unclassified

“…Piyasada birkaç firmaya ait nikotin aşısı bulunmakla birlikte henüz hiç biri sigara bırakma tedavisinde kullanılmak üzere lisans almamıştır. Bu aşılarla yapılan faz II ve faz III çalışmalarda aşıların serumda yeterince antikor oluşturamadığı tespit edilmiştir (41,45,46) . Bu aşılarda kullanılan nikotin bağlayıcı bileşikler pseudomonas aeruginosa eksotoksini, rekombinan kolera B toksini, virüs benzeri protein ve sentetik nanopartiküllerdir (41) .…”

Section: Immunoterapi (Nikotin Aşısı)unclassified

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Other Pharmacological and Developing Treatments in Smoking Cessation/Nicotine Vaccines

Salepçi¹

2017

GGHS

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“…Así, la búsqueda de terapias altamente efectivas y eficientes representa un reto para el tratamiento de las adicciones. Una alternativa a la farmacología tradicional es la inmunoterapia o vacunación dirigida a sustancias de abuso (Brimijoin, Shen, Orson, & Kosten, 2013;Kinsey, 2014;Zalewska-Kaszubska, 2015).…”

Section: Introductionunclassified

El estado actual de las vacunas contra las drogas

Matus-Ortega¹,

Nieves²,

Barbosa-Méndez³

et al. 2017

RIIAD

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Introducción: por lo común, la adicción a las drogas se trata con psicoterapia y farmacología que evita la unión de las sustancias psicoactivas a receptores específicos en el cerebro. El resultado de estos tratamientos no ha sido del todo satisfactorio, por lo que el desarrollo de terapias más eficaces representa un reto constante para tratar las adicciones. Una alternativa a la farmacología antiadictiva es la vacunación activa dirigida contra las sustancias de abuso. Objetivo: esta revisión reúne la información disponible sobre los fundamentos y avances científicos en la generación de una terapia inmunológica, que coadyuve al tratamiento de la adicción a sustancias como la heroína-morfina, la cocaína, la nicotina y la anfetamina. Método: se consideraron los reportes científicos disponibles en PubMed –de 2005 a abril de 2017–, sobre los fundamentos, la metodología empleada, los estudios preclínicos y clínicos, y los resultados obtenidos en dichas investigaciones para generar vacunas contra las drogas. Resultados: las vacunas lograron mitigar los efectos producidos por las sustancias en los estudios preclínicos en modelos de estudio en animales; sin embargo, con pacientes humanos los resultados no han sido del todo satisfactorios. Discusión y conclusiones a pesar de los esfuerzos realizados por diferentes grupos de investigación y compañías farmacéuticas para generar vacunas terapéuticas contra el uso de diferentes drogas, ninguna ha alcanzado la fase III de estudios clínicos. En la actualidad, se continúa con los esfuerzos para lograr que las vacunas contra las adicciones alcancen su máxima eficiencia y eficacia, y contribuyan al tratamiento de la adicción a las drogas.

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Vaccines against drugs of abuse: where are we now?

Cited by 32 publications

References 96 publications

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

Other Pharmacological and Developing Treatments in Smoking Cessation/Nicotine Vaccines

El estado actual de las vacunas contra las drogas

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