ABSTRACT
The cardiovascular and respiratory effects of dermorphin (D) have been evaluated in freely moving or anesthetized normotensive and spontaneously hypertensive male rats. Intravenously or intracerebroventricularly administration of D produced arterial hypotension with sinus bradycardia and respiratory depression. Naloxone antagonized the effects of D. Atrial natriuretic antipeptide IgG reduced the cardiovascular responses without any significant modification of respiratory response. ICI 174864, naloxonazine and binaltorphimine did not reduce the cardiovascular and respiratory effects. In hypertensive rats D produced more intense and longer cardiovascular effects than those seen in normotensive animals. D effects involve the activation of mu and k opioid receptors for cardiovascular responses and mu 2 opioid receptors for respiratory depression without any significant effect on delta receptors. The release of atrial natriuretic peptide also appears to be involved in the cardiovascular effects of D.
Subject(s)
Analgesics, Opioid/pharmacology , Hemodynamics/drug effects , Oligopeptides/pharmacology , Respiration/drug effects , Anesthesia , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Injections, Intravenous , Injections, Intraventricular , Male , Narcotic Antagonists/pharmacology , Opioid Peptides , Rats , Rats, Inbred SHR , Rats, Inbred StrainsABSTRACT
The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3,8-diphenyl-2H-pyrano[2,3-f]quinazolin- 2-ones by the reaction of phenylchloroketene with a series of N,N-disubstituted (E)-6-aminomethylene-7,8-dihydro-2-phenylquinazolin-5(6H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The methylbenzylamino and diphenylamino derivatives showed platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid. The 1-pyrrolidinyl derivative showed appreciable local anesthetic activity in mice, whereas the whole series of compounds exhibited weak antiinflammatory activity in rats.
