ADHD - An Illustrated historical overview

Neurotransmitters N eurotransmitters are the chemical messengers which convey mes- sages between nerve cells in the brain. A perhaps surprisingly small panel of chemicals have been selected by evo- lution to execute the complex func- tions of the central nervous system, with differences in the distribution of different receptor types and the re- sponses they induce inside the cells which carry them, and the different topographical distribution of differ- ent nervous pathways which allows the complexity of communication and response which characterizes the hu- man brain. This limited panel of neuro- transmitters has both advantages and disadvantages for the development of agents to ameliorate the effects of brain disorders. The major disadvan- tage is that even if one identifies that a chemical deficit, imbalance or other abnormal condition primarily involves a particular transmitter system, it is difficult to achieve the desired re-ad- justment by chemical means without affecting – perhaps in a negative fash- ion – other aspects of brain function. The neurotransmitter most commonly implicated in ADHD is dopamine. Once considered nothingmore than an inter- mediate product in the synthesis of the other two catecholamine transmitters, adrenaline and noradrenaline, it is now recognized that dopamine is essen- tially involved in a variety of functions, including the control and modulation of emotivity and reactivity, concentra- tion, reasoning, and the co-ordination of motor function. An abnormally low level of effective dopamine can cause the three primary symptoms of ADHD: inattention, impulsiveness, and hyper- activity. Mechanisms involved in the metabolism of dopamine may cause this low level: reduced production, in- creased re-uptake by transporter mol- ecules or catabolism, reduced receptor response to released dopamine. The fact that stimulants increase the levels of dopamine and other neurotransmit- ters (including epinephrine and sero- tonin) and help reduce ADHD symp- toms suggests that complex interac- tions between these neurotransmitters underlie ADHD. A disorder as complex as ADHD is, however, unlikely to be based upon the dysfunction of a single neural sys- tem and other transmitters may thus be involved. Noradrenaline has been implicated in animal studies as be-