Top Gene Interactions
- Metabolism: Hepatic. Cocaine is metabolized to benzoylecgonine and ecgonine methyl ester, which are both excreted in the urine. In the presence of alcohol, a further active metabolite, cocaethylene is formed, and is more toxic then cocaine itself. Half Life: 1 hour
- Uses/Sources: Cocaine (KOE-kane) is a local anesthetic. It is applied to certain areas of the body (for example, the nose, mouth, or throat) to cause loss of feeling. This allows some kinds of examinations or surgery to be done without causing pain. (L1505)
- Health Effects: Continued use produces insomnia, hyperactivity, anxiousness, agitation and malnutrition. Overdoses can be lethal.
- Symptoms: Intense agitation, convulsions, hypertension, rhythm disturbance, coronary insufficiency, hyperthermia, rhabdomyolysis, and renal impairment.
- Treatment: The specific treatment of acute cocaine poisoning is the intravenous administration of a short-acting barbiturate or diazepam. Artificial respiration may be necessary. It is important to limit absorption of the drug. If entrance of the drug into circulation can be checked, and respiratory exchange maintained, the prognosis is favorable since cocaine is eliminated fairly rapidly. (L1712)
- Route of Exposure: Cocaine is absorbed from all sites of application, including mucous membranes and gastrointestinal mucosa. By oral or intra-nasal route, 60 to 80% of cocaine is absorbed.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: Oral mouse LD<sub>50</sub> = 96 mg/kg LD50: 95.1 mg/kg (i.p, mouse) (L1860)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Muscarinic acetylcholine receptor M1
Muscarinic acetylcholine receptor M2
5-hydroxytryptamine receptor 1A
Sigma non-opioid intracellular receptor 1
Sodium channel protein type 10 subunit alpha
Sodium channel protein type 11 subunit alpha
Sodium channel protein type 5 subunit alpha
Sodium-dependent serotonin transporter
Sodium-dependent dopamine transporter
Sodium-dependent noradrenaline transporter
Kappa-type opioid receptor
D(3) dopamine receptor
D(1A) dopamine receptor
Sodium- and chloride-dependent GABA transporter 1
|Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Cocaine also produces a number of indirect actions, which alter other neuromodulatory systems (i.e., opioidergic, glutamatergic, and GABAergic systems).||