Changes

MAOA inhibitory drugs require dietary modification since they can become toxic in the presence of excess dietary tyramine. This is not the case with relatively selective MAOB inhibitors like selegiline. MAOA inhibitory drugs are NOT suitable alternatives to selegiline.

MAOA inhibitory drugs require dietary modification since they can become toxic in the presence of excess dietary tyramine. This is not the case with relatively selective MAOB inhibitors like selegiline. MAOA inhibitory drugs are NOT suitable alternatives to selegiline.

Selegiline reduces anxiety and depression mainly through its effect on dopamine. Although a selective inhibitor of MAOB, there is evidence that selegiline does also partially inhibit MAOA, so some of those anti-depressant and anti-anxiety effects probably do occur. In addition there is some further evidence that it could possibly increase dopaminergic activity by other mechanisms, these include increased synthesis and release of dopamine into the synapse and interference with re-uptake of dopamine from the synapse. (Heinonen EH, Lammintausta R: A review of the pharmacology of selegiline. Acta Neurol Scand 84:(suppl. 136):44-59, 1991 and Heikkila RE, Cabbat FS, Manzino L, et al: Potentiation by deprenil of l-dopa induced circling in nigral-lesioned rats. Pharmacol Biochem Behav 15:75-79, 1981.)  

Selegiline reduces anxiety and depression mainly through its effect on dopamine. Although a selective inhibitor of MAOB, there is evidence that selegiline does also partially inhibit MAOA, so some of the related anti-depressant and anti-anxiety effects probably do occur. In addition there is some further evidence that it could possibly increase dopaminergic activity by other mechanisms. These include increased synthesis and release of dopamine into the synapse and interference with re-uptake of dopamine from the synapse. (Heinonen EH, Lammintausta R: A review of the pharmacology of selegiline. Acta Neurol Scand 84:(suppl. 136):44-59, 1991 and Heikkila RE, Cabbat FS, Manzino L, et al: Potentiation by deprenil of l-dopa induced circling in nigral-lesioned rats. Pharmacol Biochem Behav 15:75-79, 1981.)  

*There may be some reduction in anxiety due to MAOA effects, but this is thought to be relatively small.

*There may be some reduction in anxiety due to MAOA effects, but this is thought to be relatively small.

*Dopamine level is associated with playfulness. Increased dopamine levels are linked to increased playfulness.

*Dopamine level is associated with playfulness. Increased dopamine levels are linked to increased playfulness.

*Dopaminergic neurons are concentrated in the mesocorticolimbic dopamine system of the midbrain. This is thought to be part of the reward system that somehow assigns value to adaptive behaviours. D₁ receptors are affected in mood disorders and stereotypes and manifest their post-synaptic inhibition in the limbic system. Recent experiments have shown that normal dogs treated with the drug improve their performance in certain learned tasks and it is believed that this is due to improved function of the reward system.

*Dopaminergic neurons are concentrated in the mesocorticolimbic dopamine system of the midbrain. This is thought to be part of the reward system that somehow assigns value to adaptive behaviours. Recent experiments have shown that normal dogs treated with the drug improve their performance in certain learned tasks and it is believed that this is due to improved function of the reward system.

????In the Miller model this could raise the height and perhaps increase the gradient of the approach line, whilst also lowering the avoidance line????

????In the Miller model this could raise the height and perhaps increase the gradient of the approach line, whilst also lowering the avoidance line????

*In mood disorders and stereotypies D₂, D₃ and D₄ receptors are all also affected.

*D₁ receptors are affected in mood disorders and stereotypes and manifest their post-synaptic inhibition in the limbic system. In mood disorders and stereotypies D₂, D₃ and D₄ receptors are all also affected.

*Dopamine is also important in the putative ‘seeking’ circuit, which is involved in reinforcement of search, exploratory and investigatory behaviours. Animals that have an enhancement of the ‘seeking’ system become immensely interested in what is around them and become excited when they anticipate the arrival of things that they want.

*Dopamine is also important in the putative ‘seeking’ circuit, which is involved in reinforcement of search, exploratory and investigatory behaviours. Animals that have an enhancement of the ‘seeking’ system become immensely interested in what is around them and become excited when they anticipate the arrival of things that they want.

*Two of the main metabolites of selegiline, L-amphetamine and L-methamphetamine may also play a role in its effects, however the extent to which this is the case is uncertain.

*Two of the main metabolites of selegiline, L-amphetamine and L-methamphetamine may also play a role in its effects, however the extent to which this is the case is uncertain.

Remembering that in veterinary medicine depression, anxiety and the inhibitory effects of fear are measured by observing behaviour, a drug that increases exploratory behaviour, activity, playfulness and response to appetitive events would, by definition, reduce observed levels of depression. So the effect of selegiline may in some way be to reduce fear and anxiety, whilst at the same time increasing the tendency to explore and then enhancing reward for behaviours.  

Remembering that in veterinary medicine depression, anxiety and the inhibitory effects of fear are measured by observing behaviour, a drug that increases exploratory behaviour, activity, playfulness and response to appetitive events would, by definition, reduce observed levels of depression. So the effect of selegiline may in some way be to reduce fear and anxiety, whilst at the same time increasing the tendency to explore and then enhancing reward for behaviours.  

==Use==

==Use==

:*Compulsive/stereotypical disorders [predominantly involving fear]

:*Compulsive/stereotypical disorders [predominantly involving fear]

 

==Adverse Effects==

==Adverse Effects==