Histamine receptors –
H1- Allergic responses. Watery eyes, congestion, etc. from allergies.
Anaphylaxis – bronchial larynx constriction.
Skin allergic response – reddening, rashes, welts.
Edema from injury.
H2 – Gastric secretion. Important for ulcer treatment and acid reflux
H3 – ? CNS receptors. There are also H1 receptors in the CNS.
Antihistamines are also used for motion sickness. In general their antimuscarinic effects are similar to that of scopolamine, although weaker. Antihistamines Histamine Agonists: Histamine Agonists Antihistamines – H1 Blockers: Ethylenediamines Antihistamines – H1 Blockers Antihistamine SAR: Aminoalkylethers Piperazine/N-heterocycle Series Antihistamine SAR Stereo- and regioisomers: Antihistamines are stereospecific. A
number of new, single isomer drugs are
being developed. Antihistamines are structurally similar
To SSRIs and to antipsychotics. Notice
The subtle difference between fluoxetine
And several antihistamines. Stereo- and regioisomers Alkyl Amines: Alkyl Amines Long Duration, less sedation than ethylenediamines, ethanolamines. The
“next best thing” until the “2nd generation” were developed. Rigid Analogs (I): A Cl at the 2-position weakens H1 activity relative to antimuscarinic activity and D2 antagonist activity Rigid Analogs (I) Rigid Analogs (II): Primethixene Loratadine (Claritin) Desloratadine (Clarinex) Rigid Analogs (II) Astemizole: Hismanal was FDA approved in 1988 as an antihistamine for allergy and hay fever symptom relief. The FDA first warned consumers and healthcare providers of new safety information regarding Hismanal February 9, 1998 due to the risk of death, cardiovascular adverse events, anaphylaxis, and serious drug interactions.
In addition, Hismanal labeling was changed to stress avoiding the use of Hismanal in combination with certain other medications and for liver disorder patients to completely avoid its' use.
After a series of labeling changes and warnings Hismanal was recalled on June 21, 1999. Astemizole Antihistamines “related” to butyrophenones: Terfenadine was discontinued when it became apparent that there was a high frequency of heart arrythmia associated with the drug. Fexofenadine is a metabolite and is the activated form responsible for antihistamine activity. In patients with compromised liver metabolism, or when the presence of other drugs limited the metabolism of terfenadine, persistent levels resulted in the observed arrythmias. Therefore, the fexofenadine replaced terfenadine (1997).
Ventricular Arrythmias are not good! Antihistamines “related” to butyrophenones Butyrophenone-like structures: Butyrophenone-like structures Allegra Propaganda - www.allegra.com: Allegra Propaganda - www.allegra.com www.zyrtec.com: If you haven't gotten the relief you want from Claritinｨ (loratadine), Clarinexｨ (desloratadine), or Allegraｨ (fexofenadine HCl), ask your doctor if ZYRTEC is right for you. www.zyrtec.com Structural Summary: Linking the first generation with Non-sedative Antihistamines.
Big Picture - Bottom Line Structural Summary Anti-emetics: Anti-emetics Anti-emetic Table: Synthetic
Tropane Alkaloids Anti-emetic Table 2005 Nobel Prize: Press Release: The 2005 Nobel Prize in Physiology or Medicine
3 October 2005
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine for 2005
Barry J. Marshall and J. Robin Warren
for their discovery of
"the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease” 2005 Nobel Prize Gastric Secretions Cell Biology: Gastric Secretions Cell Biology H2 Histamine antagonists.: Gastric receptors are pharmacologically distinct. The classic H1 antagonists don’t interact with H2 receptors. Antihistamines are an important treatment for gastric disorders; antacids, ulcer treatment, acid-reflux disease. H2 Histamine antagonists. H2 Histamine antagonists. - Structures: H2 Histamine antagonists. - Structures