Drugs acting by inhibition or activation of receptors for dopamine, serotonine and

histamine

Practice pharmacology,

medical students III.yr.

November 2013

Dopamine and dopamine receptorsEffect of antagonists of dopamine

A/ Antipsychotic effect

1/ Typical antipsychotics (1. generation): chlorpromazin, haloperidol 2/ Atypical antipsychotic agents (2. generation):

a/ clozapin, olanzapin, risperidon, ziprasidon, quetiapineb/ sulpirid and amisulpirid: D2, D3 antagonists

3/ Dopaminergic „stabilisator“ = presynaptic agonist/postsynaptic

antagonist of D2 receptor and 5-HT2 antagonist aripiprazol

B/ Antiemetic effect metoclopramid, domperidon, itoprid

Drugs used in the treatment of Parkinson´s disease

1. Agonists of dopamine receptors: bromokriptin /D2/, ropinirol, pramipexol, rotigotine

2. Inhib. of MAO-B: selegilin, cannot be combined with L-DOPA

3. COMT inhibitors: entacapon

4. L-DOPA

SEROTONIN, (5-HYDROXYTRYPTAMIN, 5-HT)• Serotonine receptors: 5HT1A, 5-HT2, 5-HT3, 5-HT „xyz“

Clinical effects of activation/inhibition of serotonine receptors

5HT-1A agonist = anxiolytic and antidepressant eff.

5-HT2 antagonist eff. = antipsychotic eff., improvement of

sleep

• 5-HT3 antagonists: antiemetic effects

ondansetron, granisetron, tropisetron etc.

• 5-HT1A agonist: buspiron - anxiolytic drug, approved indication GAD, can be used also as add-on for alcoholics, with care as add-on to some antidepressant medication

• 5-HT1D (1B) agonists: antimigrenic effects

sumatriptan, naratriptan, zolmitriptan etc.

Antidepressants blocking serotonine receptors

• 5-HT2• Agomelatine =

agonist at melatonine receptors and antagonist at 5-HT2 rcp.

(should not be combined with alcohol, regular control of AST and ALT is necessary)

• 5-HT-2 and 5-HT-3

• Mirtazapine = noradrenergic and specific serotoninergic antidepressant

HISTAMINE and histamine receptors

• Histamine receptors H1, H2 and H3 • Antagonists of H1 receptors alleviate

symptoms of alergic reactions, can have antiemetic, sedative effects

• 1/ Sedative – promethazin, hydroxyzin (hydroxyzine is biotransformed to cetirizine), bisulepine etc.

• 2/ Not sedative – cetirizine and levocetirizine, loratadine and desloratadine

• 3/ Not sedative antihistaminic drug blocking effect of PAF /platelet activ. factor/ = rupatadin /rupatadine is metabolised to desloratadine/

Histamine and histamine receptors

• Antagonists of H2 receptors

- ranitidine, famotidine,

(historical example cimetidine)

• Antagonists of H3 receptors = betahistin for Meniere disease and problems like tinnitus, hearing loss

Questions

1/ Treatment with antagonists of histamine H1 receptor is symptomatic or causal therapy of allergic diseases?

It is symptomatic treatment.

2/ What antihistamine drugs can be considered as immunomodulatory (= can have antiinflammatory effect) and why? levocetirizine, desloratadine and rupatadine: clinically these drugs will have also some effect on nasal obstruction

(levocetirizine inhibits migration of eosinophils to the site of allergic reaction, desloratadine inhibits expression of adhesion molecules or inflammatory cytokines, rupatadine blocks also effect of PAF in addition to ihibitory effects on histamine release)

3/ What are possible combinations of antihistaminic drugs with other drugs for treatment of allergy in clinical practice?E.g.: cetirizine+mometasone (local corticosteroid); desloratadine+montelukast (both p.o.)