Cocaine Metabolites

(Benzoylmethylecgonine, an ecgonine derivative) is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" and the alkaloid suffix "-ine", forming "cocaine". It is a stimulant, an appetite suppressant, and a nonspecific voltage gated sodium channel blocker, which in turn causes it to produce anesthesia at low doses. Biologically, cocaine acts as a serotonin–no repinephrine–dopamine reuptake inhibitor, also known as a triple reuptake inhibitor (TRI). It is addictive because of its effect on the mesolimbic reward pathway. It is markedly more dangerous than other CNS stimulants, including the entire amphetamine drug class, at high doses due to its effect on sodium channels, as blockade of Nav1.5 can cause sudden cardiac death.

Cocaine is a powerful nervous system stimulant. Its effects can last from 15–30 minutes to an hour, depending on dosage and the route of administration. Cocaine increases alertness, feelings of well-being and euphoria, energy and motor activity, feelings of competence and sexuality. Anxiety, paranoia and restlessness can also occur, especially during the comedown. With excessive dosage, tremors, convulsions and increased body temperature are observed. Severe cardiac adverse events, particularly sudden cardiac death, become a serious risk at high doses due to cocaine's blocking effect on cardiac sodium channels. Occasional cocaine use does not typically lead to severe or even minor physical or social problems. With excessive or prolonged use, the drug can cause itching, tachycardia, hallucinations, and paranoid delusions. Overdoses cause hyperthermia and a marked elevation of blood pressure, which can be life-threatening, arrhythmias, and death.

Chronic cocaine intake causes brain cells to adapt functionally to strong imbalances of transmitter levels in order to compensate extremes. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an "off" or "working mode" respectively, or they change their susceptibility for binding partners (ligands) – mechanisms called down-up regulation. However, studies suggest cocaine abusers do not show normal age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuro protective properties for dopamine neurons