?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Optimal+Agonist%2FAntagonist+Combinations+Maintain+Receptor+Response+by+Preventing+Rapid+beta1-Adrenergic+Receptor+Desensitization&rft.creator=Lanzara%2C+Richard&rft.subject=Neuropharmacology&rft.description=Desensitization+is+a+serious+side+effect+of+many+drugs.+It+is+also+a+fundamental+problem+for+modeling+drug-receptor+interactions.+This+study+was+designed+to+test+a+receptor+model+and+a+method+to+optimize+agonist%2Fantagonist+combinations+calculated+to+prevent+receptor+desensitization%2C+which+has+relevance+for+many+important+drugs%2C+including+the+b1-adrenergic+agonist+drugs.++Because+desensitization+is+a+serious+side+effect%2C+the+beta1-adrenergic+agonist+drugs+are+no+longer+the+logical+treatment+for+heart+failure+and+have+been+replaced+by+antagonist+drugs+represented+by+metoprolol+(Lopressor).++Although+the+scientific+rationale+for+this+remains+unclear+and+because+the+agonist+and+antagonist+drugs+may+be+administered+together+in+some+medical+circumstances%2C+it+is+important+to+understand+the+early+interactions+of+beta-agonist+drugs+with+the+beta-antagonist+drugs+at+the+level+of+the+initial+receptor+response.+Isoproterenol+(Iso)+or+dobutamine+(Dob)+were+given+as+intravenous+solutions+to+rats+with+or+without+the+beta1-antagonist%2C+metoprolol+(Met)%2C+which+was+given+either+as+a+fixed+amount+or+as+part+of+an+agonist%2Fantagonist+combination.+The+Iso+and+Dob+solutions+alone+demonstrated+rapid+desensitizaton%2C+whereas+the+optimal+Iso%2FMet+and+Dob%2FMet+agonist%2Fantagonist+combinations+significantly+prevented+desensitization+while+maintaining+near+maximal+responses+in+all+of++the+animals+tested.+The+theory+behind+the+model+predicted+these+responses+and+fit+the+experimental+data+with+reasonable+biophysical+parameters.+This+study+supports+the+concept+that+the+earliest+events+of+receptor+desensitization+can+be+modeled+and+controlled+at+the+level+of+the+initial+receptor+response+and+also+suggests+that+the+beneficial+effects+of+metoprolol+for+heart+failure+may+result+from+its+action+on+the+earliest+events+of+receptor+activation.+&rft.publisher=ANSInet+(Asian+Network+for+Scientific+Information)&rft.contributor=Sarwar%2C+Muhammad&rft.date=2005-01&rft.type=Journal+(Paginated)&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F4093%2F1%2FLanzaraIJP.pdf&rft.identifier=++Lanzara%2C+Richard++(2005)+Optimal+Agonist%2FAntagonist+Combinations+Maintain+Receptor+Response+by+Preventing+Rapid+beta1-Adrenergic+Receptor+Desensitization.++%5BJournal+(Paginated)%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F4093%2F