2,5-Dimethoxy-4-Methylamphetamine

/LABORATORY ANIMALS: Acute Exposure/ The characteristics of the behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM or STP) were compared with those of mescaline and methamphetamine in rats and mice. DOM significantly increased locomotor activity in an open-field situation at 0.5-1.0 mg/kg ip, but at doses above 5 mg/kg ip caused biphasic changes, i.e. an initial decrease followed by an increase in motility and exploratory behavior. This hyperactivity was not accompanied by simultaneous increase in rearing. Besides, DOM induced head twitches in rats as well as in mice at doses above 0.1 mg/kg ip, and marked backward locomotion only in rats at doses larger than 5 mg/kg ip. The occurrence of backward locomotion might be attributable to the initial decrease in general activity. Behavioral effects of DOM were different from those of either mescaline or methamphetamine although they resembled those of mescaline in some respects.

/LABORATORY ANIMALS: Acute Exposure/ A single dose of 2,5-dimethoxy-4-methylamphetamine (DOM) (246 ug/kg) produced a pressor response in vagotomized dogs. There was also an increase in pulse pressure. Tachyphylaxis developed rapidly after repeated doses of DOM. Responses to tyramine were not diminished after tachyphylaxis to DOM developed. DOM also enhanced pressor responses to norepinephrine, epinephrine and tyramine. ...

/ALTERNATIVE and IN VITRO TESTS/ ... In isolated guinea-pig atria, DOM exhibited an antinicotine action and also blocked the inhibitory effect induced by vagus nerve stimulation. ...

/ALTERNATIVE and IN VITRO TESTS/ The uptake of 2,5-dimethoxy-4-methylamphetamine (DOM, STP) into rabbit blood platelets and the effect of DOM on uptake and release of 5-hydroxytryptamine (5-HT) from platelets have been investigated. Tritium labeled DOM was taken up slightly against the concentration gradient. DOM in concentrations ranging from 5.0 X 10-5 to 1 X 10-3 M did not affect 14C-5-HT uptake into platelets. However, it increased the 14C-5-HT release from platelets by 100 and 300% at 2 X 10-4 and 1 X 10-3 M respectively when platelets were incubated in Krebs-Ringer phosphate buffer, but exerted no effect on the release of 14C-5-HT from the platelets when incubated in 0.9% saline. ...

... Phenylisopropylamines as a class interact with CYP2D6 as substrates and/or inhibitors. Their use may cause metabolic interactions with other drugs that are CYP2D6 substrates, and the potential for polymorphic oxidation via CYP2D6 may be a source of interindividual variation in their abuse liability and toxicity.

While data specific to 4-methyl-2,5-dimethoxyamphetamine were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Maintain an open airway and assist ventilation if necessary. Treat agitation, seizures, coma, and hyperthermia if they occur. Benzodiazepines are usually satisfactory for treatment of agitation, although butyrophenones may also be used. Continuously monitor the temperature, other vital signs, and ECG for a minimum of 6 hours. There is no specific antidote. Hypertension is best treated by sedation and, if this is not effective, a parenteral vasodilator such as phentolamine or nitroprusside. Treat tachycardia with propranolol or esmolol. ... Decontamination: administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Consider whole-bowel irrigation and repeat doses of charcoal after ingestion of drug filled packets ("body stuffers"). Enhanced elimination: Dialysis and hemoperfusion are not effective. Repeat-dose charcoal has not been studied. ... /Amphetamines/

LD50 Mouse ip 89 + or -4.2 mg/kg /hydrochloride/

LD50 Mouse ip 94 mg/kg

LD50 Rabbit oral 200 mg/kg

In an effort to more fully characterize the metabolic fate of the psychotomimetic amine (1-(2, 5-dimethoxy-4-methylpheny)-2-aminopropane (DOM, STP), the formation of the two possible monophenols and the p-hydroquinone metabolites of the parent drug by 10,000 X g supernatent fractions of rabbit liver homogenates has been investigated. All three metabolites have been fully characterized and quantitatively estimated by chemical ionization mass spectrometry with the aid of deuterium enriched compounds. The stereochemical course of the mono-O-demethylation reactions has been shown to proceed with enantiomeric enrichment of the S-aminophenols. The mechanistic implications concerning the mode of action of the parent drug and metabolic O-demethylation are discussed.

The possible relationship between metabolism and psychotomimetic activity among the methoxylated 1-phenyl-2-aminopropanes led to our investigation of the in vitro O-demethylation of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (1, DOM, STP). Employing a sensitive and highly selective stable isotope dilution assay, we observed that rabbit liver homogenates biotransform the amine 1 to its 2-O-demethyl, 5-O-demethyl, and bis (O-demethyl) metabolite metabolites. Both monophenolic metabolites are enriched in their S enantiomers. The bis(O-demethyl) metabolite has structural, chemical, and electrochemical similarities to the sympatholytic agent "6-hydroxydopamine". The possible significance of metabolic O-demethylation in terms of the psychotomimetic properties of amine 1 is discussed.

Metabolites of STP have been synthesized and identified in rat urine and feces. A 4-hydroxymethyl compound which resulted from hydroxylation of the 4-methyl group of STP accounted for half of the total amount of the metabolites isolated in the 24 hour urine. The further oxidation product of the 4-hydroxymethyl compound, the 4-carboxy metabolite and unchanged STP were present in a ratio of 2 to 7. A trace amount of the ketone, derived from oxidation of the side-chain of STP, was also detected. The feces at the same time interval contained almost exclusively the 4-carboxy metabolite, with the 4-hydroxymethyl metabolite and a relatively small quantity of unchanged STP amounting to less than 7%. In the present study /investigators/ attempted to isolate metabolites of STP in monkey and rat brains, as well as in regional areas of the monkey brain for any possible correlation between metabolism and and the behavioral effects.

The designer drug 2,5-dimethoxy-4-methyl-amphetamine (DOM, STP) is known to be extensively metabolized in various species. The current study showed that cytochrome P450 2D6 was the only isoenzyme involved in formation of the main metabolite hydroxy DOM. In addition, the authors' systematic toxicological analysis (STA) procedure using full-scan GC-MS was suitable to prove an intake of a common drug users' dose of DOM by detection of hydroxy DOM in rat urine. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of DOM in human urine. However, DOM and/or other metabolites such as deamino-oxo-hydroxy DOM might be the target analyte in urine of CYP2D6 poor metabolizers.

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.