Blockade of a cardiac K+ channel by tacrine: interactions with muscarinic and adenosine receptors
| Autor: | Shirley Estelle Freeman, Maria Szilagyi, Wai-Man Lau |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
medicine.medical_specialty
Adenosine Potassium Channels Carbachol Guinea Pigs Action Potentials In Vitro Techniques Pharmacology Guinea pig Alzheimer Disease Internal medicine Muscarinic acetylcholine receptor medicine Animals Aminoacridines Chemistry Receptors Purinergic Heart Myocardial Contraction Receptors Muscarinic Adenosine receptor Quinuclidinyl Benzilate Electrophysiology Endocrinology Mechanism of action Tacrine Phenylisopropyladenosine medicine.symptom medicine.drug |
| Zdroj: | European Journal of Pharmacology. 154:59-65 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(88)90363-9 |
| Popis: | The centrally acting anticholinesterase drug tacrine has been shown to block K + channels in guinea pig left atrium. It competitively blocks the negative inotropic effects of adenosine, 2-chloroadenosine and carbachol. K a values obtained from dose ratio plots were 2.5, 3.5 and 2.9 μM respectively. It was also able to antagonize the shortening of the action potential due to these compounds. Doses of tacrine ranging from 1 to 4 μM restored the AP configuration close to control values. Tacrine also antagonized the binding of 1-quinuclidinyl[phenyl-4- 3 H]benzilate ([ 3 H]QNB) to membranes derived from the atrium and cerebral cortex. K i values of 1.8 ± 0.33 and 1.3 ± 0.47 μ M were obtained respectively. Tacrine was a weak competitor of [ 3 H]phenylisopropyladenosine ([ 3 H]L-PIA) binding in brain membranes. Its diverse pharmacological effects may be relevant to its use in Alzheimer's disease. |
| Databáze: | OpenAIRE |
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