Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
165 l. : il., tab. ; 30 cm
Ad1) Sledování vlivu antidepresiv citalopramu a desipraminu v animálním modelu na potkanech na farmakokinetiku syntetických drog 2C-B a DOB. Tato antidepresiva budou snižovat hladiny drog v plicní a mozkové tkáni. Měření bude provedeno pomocí GC-MS. Ad 2) Zavedení metodiky pro stanovení drog 2C-B a DOB použitelné v klinické praxi. Ad 3) Změny v chování potkanů po akutním podání 2C-B a DOB a jejich ovlivnění citalopramem a desipraminem. Antidepresiva antagonizují behaviorální změny po 2C-B a DOB (měřenílokomoce a test prepulzní inhibice akustické úlekové reakce). Ad 4) Sledování změn v kvantitativním EEG potkanů vyvolaných akutním podáním 2C-B a DOB a jejich ovlivnění citalopramem a desipraminem. Antidepresiva budou antagonizovat změny v kvantitativnímEEG zvířat.; Ad 1) Monitoring of the effects of antidepressants citalopram and desipramin on the pharmacokinetics of 2C-B and DOB in animals. These antidepressants will decrease tissue levels of drugs in the lungs and the brain. Analyses will be done by GC-MS. Ad 2)Development of the method for 2C-B and DOB detection usable in the clinical practice Ad 3) Analysis of behavioral changes in rats after acute 2C-B and DOB treatment and the influence of citalopram and desipramine. Antidepressants will antagonize 2C-B andDOB induced behavioral changes (locomotion and prepulse inhibition of acoustic startle). Ad 4) Analysis of quantitative EEG in rats after acute 2C-B and DOB and the influence of citalopram and desipramin. Antidepressants will antagonize changes in quantitative EEG.
- MeSH
- 2,5-dimethoxy-4-methylamfetamin farmakokinetika MeSH
- alfa-adrenergní receptory MeSH
- behaviorální symptomy MeSH
- citalopram farmakologie MeSH
- desipramin farmakologie MeSH
- dimethoxyfenylethylamin analogy a deriváty farmakokinetika MeSH
- elektroencefalografie metody využití MeSH
- krysa rodu rattus MeSH
- modely u zvířat MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- Check Tag
- krysa rodu rattus MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- neurologie
- psychofarmakologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : tab. ; 30 cm
Pomocí rozšířených toxikologických metod na principu GC-MS bude sledována biotransformace některých rizikových ilegálních syntetických drog. Pokusným potkanům budou podány vybrané noxy per os, sbírány frakce moče a v nich určovány vylučované metabolity.; The biotransformation of selected illegal synthetic drugs will be studied using toxicological methods based on GC-MS. After administration of toxic agents to experimental rats, excreted urine will be collected, and structure of metabolites determined.
- MeSH
- 2,5-dimethoxy-4-methylamfetamin metabolismus MeSH
- 3,4-methylendioxyamfetamin metabolismus MeSH
- amfetaminy farmakologie metabolismus škodlivé účinky MeSH
- biotransformace MeSH
- epidemiologické metody MeSH
- experimenty na lidech MeSH
- experimenty na zvířatech MeSH
- metabolická clearance MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody využití MeSH
- soudní toxikologie MeSH
- zakázané drogy MeSH
- Publikační typ
- kazuistiky MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmacie a farmakologie
- toxikologie
- biochemie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
The psychedelic compound 4-bromo-2,5-dimethoxyphenethylamine (2C-B) has appeared as an agent in drug abuse or overdose cases in humans. The human pharmacokinetics of this drug is unknown and only partial information is available on its metabolites. Our experimental study was focused on the disposition and kinetic profile of 2C-B in rats after subcutaneous administration using a GC-MS validated method. One of the major metabolites 4-bromo-2-hydroxy-5-methoxyphenethylamine (2H5M-BPEA) was confirmed in rat tissues of lung, brain, liver and was quantitatively evaluated as well. The disposition of 2C-B was characterized by its estimated half-life 1.1h and estimated volume of distribution 16L/kg. The lung susceptibility for drug retention and gradual temporal release parallel to the brain were ascertained. The drug penetrating the blood/brain barrier was without significant delay. 2C-B brain to serum ratio attained a maximum value of 13.9 and remained over the value of 6.5 to the end of our observation (6h after the dose). The distribution of the hydroxylated metabolite 2H5M-BPEA into the lipophilic brain tissue was less efficient in relation to the parent compound. The kinetics of the drug partitioning between blood to brain may be important for the subsequent assessment of its psychotropic or toxic effects.
- MeSH
- 2,5-dimethoxy-4-methylamfetamin analogy a deriváty farmakokinetika krev MeSH
- aplikace kožní MeSH
- dimethoxyfenylethylamin analogy a deriváty farmakokinetika krev MeSH
- financování organizované MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- mozek metabolismus MeSH
- plíce metabolismus MeSH
- potkani Wistar MeSH
- psychotropní léky farmakokinetika krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
2,5-Dimethoxy-4-bromoamphetamine (DOB) is one of the potent hallucinogenic phenylalkylamines, whose ingestion has already caused several deaths reported all over the world. However, there is insufficient information on DOB properties based on controlled pharmacokinetic studies available. The aim of this study was to clarify the distribution profile of DOB and its phenolic metabolite 2-methoxy-5-hydroxy-4-bromoamphetamine (2M5H4BA) in blood and biological tissues of experimental rats. The rats were administered a 20 mg/kg dose of DOB.HCl by oral ingestion or subcutaneous injection. Plasma and brain, liver and lung tissues were collected at 0.5, 1, 2, 4, 8, 16, and 32 h after dosing (three animals per time point). The samples were prepared by a liquid-liquid extraction procedure and the extracts were assayed by GC-MS. After per oral application, DOB peak plasma level of 320 ng/mL was reached after one-hour post dosing as well as 2M5H4BA peak concentration of 203 ng/mL. A rapid phase of DOB absorption, 2M5H4BA formation and their tissue distribution during the first two hours after application were followed by a slow decrease rate of the elimination process until 32 h. After subcutaneous application, high plasma levels of the unchanged parent drug and relatively reduced formation of its metabolite 2M5H4BA were observed. DOB maximum plasma concentration of 1143 ng/mL was reached after one-hour post application, whereas its metabolite peak level after 8 h was 213 ng/mL. The concentration profiles of both compounds in plasma after per oral and subcutaneous administration revealed the existence of significant first pass effect after per oral administration that significantly affected DOB bioavailability. DOB tissue concentrations exceeded plasma and the highest values were found in the lungs, where drug accumulation occurred with prolonged retention till 32 h after subcutaneous dose. Although the plasma/tissue transfer was more effective for the lipophilic parent drug than for its hydroxylated metabolite 2M5H4BA, the metabolite tissue levels were significant. The hallucinogenic potential of 2M5H4BA appearing in brain remains unclear as nothing is known about its pharmacological activity at present.
- MeSH
- 2,5-dimethoxy-4-methylamfetamin aplikace a dávkování analogy a deriváty farmakokinetika krev MeSH
- aplikace orální MeSH
- financování organizované MeSH
- halucinogeny aplikace a dávkování farmakokinetika krev MeSH
- injekce subkutánní MeSH
- játra chemie MeSH
- krysa rodu rattus MeSH
- mozek - chemie MeSH
- plíce chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- potkani Wistar MeSH
- soudní toxikologie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
The study of the biotransformation of a new synthetic drug 2,5-dimethoxy-4-bromamphetamine (DOB) and identification of its metabolites in urine of a poisoned person is described using gas chromatography mass spectrometry (GC-MS) with various ways of derivatization. It has been confirmed that one of its metabolic pathways leads to the corresponding 2-O-desmethyl and 5-O-desmethyl metabolites when the latter is prevailing. It is important to know the metabolism of this neurotoxic and hallucinogenic substance as it is a prerequisite for developing reliable toxicological diagnostic procedures and for assessment of toxicological risks.
