2Farma dopamine

Organization of dopaminergic system (DA)

1) 5 metabotropic receptor subtypes to which it binds (D1-D5)
 -> D1-R: stimulation of adenylate cyclase (AC)

 ->D2-R: inhibition of adenylate cyclase (AC)
  ~D2 can function as autoreceptor & as receptor

2) 3 dopaminergic systems

3) Different subsets of VTA dopaminergic neurons mediate effects of rewarding/aversive stimuli

Dopaminergic systems

1) Ultrashort system (to retina & bulbus olfactorius)

2) Intermediary system
 ->to hypophysis (pituitary), hypothalamus & medulla oblongata

 

3) Long system
1. Substantia nigra ->striatum (nigrostratial projections [path])

2. Ventral tegmentum (VTA/ventral tegmental area)
 ->frontal & limbic cortex (mesocortical projections)
 ->limbic structures (mesolimbic projections)

DA: long system

=big role in reward-system (eg activation when looking at person you like)
 ->drugs: activation long system gives addicting effect

Subsets VTA dopaminergic neurons

1) Reward-mediating pathway:
 1. input from laterodorsal tegmentum (LDT)
 2. to VTA, dopaminergic output from VTA
 3. to nucleus accumbens (NAc)

2) Aversion-mediating pathway:
 1. input from lateral habenula (LHb)
 2. to VTA, dopaminergic output from VTA
 3. to medial prefrontal cortex (mPFC)

Dopaminergic neurotransmission

1. DA stored in synaptic vesicles with help of VMAT

2. When released: enters synaptic cleft & binds to D-receptors

 

3. Production/inhibition of production of cAMP
 ->when produced: activation of protein-kinase

 

4. Protein-kinase phosphorylates translationfactor CREB

 ->influences gene expression

 ->inactivated by reuptake or breakdown by MAO or COMT

Dopaminergic drugs

(drugs which affect dopaminergic system)

1) Antipsychotics Vb. DA blockers

2) Anxiolytics Vb. Noradrenaline and DA antagonists

3) Antidepressives: potentiate DA & NA transmission Vb. MAO-I

4) Stimulants

5) Drugs for treating Parkinson’s disease Vb. L-DOPA, MAO-I, D2-agonist

Drugs with similar primary mechanism p20-21

~can differ in several ways which influence their clinical applications, including:
1) Side effects & patient tolerability

2) Pharmacokinetics (eg rates of drug absorption/metabolism)

3) Suitability for the desired route of administration

4) Additional mechanisms of action not shown in the table

5) Potential for abuse