Effect of Cocaine

Cocaine, which blocks the uptake of catecholamines, produces dose-dependent effects, initially causing euphoria, vasoconstriction, and tachycardia, and in toxic doses, convulsions, myocardial depression, ventricular fibrillation, medullary depression, and death. Cocaine is able to block nerve conduction and currently is used only for topical anesthesia. 

---

There is some evidence of a synergistic effect on reinforcement with concurrent administration of benzodiazepines and opioids (Walker and Ettenberg 2003). Cocaine abusers are less likely than opioid abusers to abuse benzodiazepines, preferring alcohol and opioids as secondary drugs of abuse. The most common pattern of benzodiazepine misuse in these individuals is intermittent use of therapeutic or supratherapeutic doses to counter unwanted effects of cocaine. 

Ahmad K Asia grapples with spreading amphetamine abuse. Lancet 361 1878—1879,2003 Almodovar-Fabregas LJ, Segarra O, Colon N, et al Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation. Ann N Y Acad... 

Large or quickly repeating doses over a period of hours can led to extreme anxiety, paranoia and even hallucinations. These effects usually disappear as the drug is eliminated from the body. The after-effects of cocaine and crack use may include fatigue and depression as people come down from the high. Excessive doses can cause death from respiratory or heart failure but this is rare. 

Arnold, L.E. Kirilcuk, V. Corson, S.A. and Corson, E.O. Levoampheta-mine and dextroamphetamine Differential effect on aggression and hyperkinesis in children and dogs. Am J Psychiatry 130 165-170, 1973. Bain, G.T., and Kometsky, C. Naloxone attenuation of the effect of cocaine on rewarding brain stimulation. Life Sci 40 1119-1125, 1987. 

The similarities in acute neurochemical effects of cocaine and amphetaminelike compounds raise the possibility that repeated exposure to cocaine might... 

Taylor, D., and Ho, B.T. Neurochemical effects of cocaine following acute and repeated injection. J Neurosci Res 3 95-101, 1977. 

Cardiovascular effects of cocaine An autopsy study of 40 patients. Am Heart J 115 1068-1076, 1988. 

Taube, H.D. Montel, H. Hau, G. and Starke, K. Phencyclidine and ketamine Comparison with the effect of cocaine on the noradrenergic neurones of the rat brain cortex. Naunvn Schmi edeberas Pharmacol 294 47-54, 1975. 

Nation JR, Liver,ore CL, Burkey RT. 1996. Chronic lead exposure attenuates sensitization to the locomotor-stimulating effects of cocaine. Drug Alcohol Dependence 41 143-149. 

Figure 1.1 The dopamine transporter terminates the action of released dopamine by transport back into the presynaptic neuron. Dopamine transport occurs with the binding of one molecule of dopamine, one chloride ion, and two sodium ions to the transporter the transporter then translocates from the outside of the neuronal membrane into the inside of the neuron.22 Cocaine appears to bind to the sodium ion binding site. This changes the conformation of the chloride ion binding site thus dopamine transport does not occur. This blockade of dopamine transport potentiates dopaminergic neurotransmission and may be the basis for the rewarding effects of cocaine.

Heikkila, R.E., Manzino, L., and Cabbat, F.S., Stereospecific effects of cocaine derivatives on 3H-dopamine uptake correlations with behavioral effects, Subst. Use Misuse, 2, ff5, f98f. 

Bergman, J., Madras, B.K., Johnson, S.E., and Spealman, R.D., Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys, J. Pharmacol. Exp. Then, 251, 150, 1989. 

Chiamulera, C., Epping-Jordan, M.R, Zocchi, A. et al. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat. Neurosci. 4 873, 2001. 

Witkin, J.M. Blockade of the locomotor stimulant effects of cocaine and methamphetamine by glutamate antagonists. Eife Sci. 53 PL405, 1993. 

Haile, C.N., GrandPre, T., Kosten, T.A. Chronic unpredictable stress, but not chronic predictable stress, enhances the sensitivity to the behavioral effects of cocaine in rats. Psychopharmacology. 154 213, 2001. 

An alternative pharmacotherapy for cocaine dependence currently under investigation is use of a cocaine vaccine to blunt the reinforcing effects of cocaine.51 60 The basis of this pharmacotherapy is to decrease the rate of entry of cocaine into the CNS (and therefore the onset of action), by either binding cocaine with antibody generated by active immunization with a stable cocaine conjugate or by using an enzymatically active antibody specific for cocaine. 

Hitri A., Little K., Ellinwood D. Effect of cocaine on dopamine transporter receptors depends on routes of chronic cocaine administration. Neuropsychopharmacology. 14 205, 1996. 

Carrera M., Ashley J., Parsons L., Wirschung P., Koob G. Suppression of psycho-active effects of cocaine by active immunization. Nature. 378 727, 1995. 

Rocio M., Carrera A., Ashley J., Wirsching P., Koob G., Janda K. A second-generation vaccine protects against the psychoactive effects of cocaine. PNAS. 98 1988, 2001. 

Shippenberg T., Heidbreder C. Sensitization to the conditioned rewarding effects of cocaine pharmacological and temporal characteristics. J. Pharmacol. Exp. Ther. 273 808, 1995. 

Meador-Woodruff J., Little K., Damask S., Mansour P., Watson S. Effects of cocaine on dopamine receptor gene expression A study in the postmortem human brain. Biol. Psychiatry. 34 348, 1993. 

---