Mescalina

Efectos

Mecanismo de acción

Hallucinogens, including mescaline, psilocybin and lysergic acid diethylamide (LSD), profoundly affect perception, cognition and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, however closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural circuits mediate their effects are poorly understood. By genetically expressing 2AR only in cortex, we show that 2AR-regulated pathways in cortical neurons are sufficient to mediate the signaling pattern and behavioral response to hallucinogens. Both hallucinogenic and non-hallucinogenic 2AR agonists regulate signaling in the same cortical neurons that express 2AR. However, signaling and behavioral responses to hallucinogens are distinct. While lisuride and LSD both act on 2AR expressed by cortical neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric G(i/o) proteins and Src. These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens. The mechanism of action of mescaline is unknown. It is believed that the hallucinogenic effects are due to stimulation of serotonin and dopamine receptors in the CNS. Mescaline (3,4,5-trimethoxyphenethylamine; MES) and its analogs, anhalinine (ANH) and methylenomescaline trimer (MMT) were investigated, using frog sciatic-sartorius preparations and rat cortical tissue. The effects of MES and its analogs were examined with respect to muscle contraction, resting membrane potential and nicotinic receptor binding. Mescaline and its analogs (10-100 microM) blocked both directly and neurally evoked contractions but their effects on neurally evoked contractions were greater than those on directly evoked contractions. Mescaline, ANH and MMT decreased the amplitude of miniature end-plate potentials and end-plate potentials, decreased the quantum content of acetylcholine (ACh), hyperpolarized the resting

Toxicidad

Mescaline (25 mg/kg; 66 μg/kg) was injected (ip) in mice 45 min before chlorpromazine (2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head movement were observed 30 min after mescaline and continued for 30-45 min afterwards; locomotor activity and the number of scratching events were significantly increased during this period. Chlorpromazine (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; chlorpromazine-sulfoxide (15 mg/kg) was not effective. The increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of chlorpromazine and thioridazine; at higher doses, both chlorpromazine (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of chlorpromazine and a higher dose of thioridazine (45 mg/kg); chlorpromazine-sulfoxide and lower doses of thioridazine had no effect. For patient with a "bad trip" or panic reaction, provide gentle tranquilization and relaxation techniques in a quiet environment. Treat agitation or severe anxiety states with diazepam or midazolam. Butyrophenones such as haloperidol are useful despite a small theoretical risk of lowering seizure threshold. Treat seizures, hyperthermia, rhabdomyolysis, hypertension and cardiac arrhythmias if they occur. /LSD and other hallucinogens/ Specific Drugs and Antidotes: There is no specific antidote. Sedative doses of diazepam may relieve anxiety, and hypnotic doses may induce sleep for the duration of the "trip". /LSD and other hallucinogens/ Decontamination: Most of these drugs are taken orally in small doses, and decontamination procedures are relatively ineffective and would probably aggravate psychological stress. Consider the use of activated charcoal

Farmacología

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations and other alterations of mood and thinking. Despite the name, the distinguishing feature of these agents from other classes of drugs is their capacity to induce states of altered perception, thinking 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. Mescaline binds to hepatic proteins but not to plasma proteins. It is rapidly and widely distributed in peripheral tissues. The volume of distribution is not specifically known but is believed to be on the order of several L/kg. Sixty percent of mescaline is excreted unchanged in 24-hour urine, and the remainder is excreted as metabolites. Peyote is rapidly absorbed after ingestion. The onset of action is between 30 minutes and 2 hours, and peak blood levels occur 2 hours after ingestion. The duration of effect usually varies from 6 to 12 hours but may last up to 14 hours. /Peyote/