Publication

α1/α2-Adrenoceptor agonist selectivity of mono- and dihydroxy-2-N,N-di-n-propylaminotetralins

Timmermans, P. B. M. W. M., Mathy, M. J. & Wilffert, B., 20-Nov-1984, In : European Journal of Pharmacology. 97, 1-2, p. 55-65 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

The pressor activities and the identity of the postjunctonal α-adrenoceptors involved were determined for a series of congeneric mono- and dihydroxy-substituted 2-N,N-di-n-propylaminotetralins and N,N-di-n-propyldopamine (DPDA) following i.v. administration to pithed normotensive rats. The affinity for α1- and α2-adrenoceptor-like binding sites was obtained from radioligand displacement studies. The 5- and 7-OH substituted tetralins as well as DPDA were reasonably potent and about equieffective pressor agents. The 6-OH congener had almost no vasoconstrictor effects whereas the 8-OH positional isomer occupied an intermediate position. The 5,6- and 6,7-di-OH analogs very effectively raised the diastolic pressure of pithed rats. On account of the inhibition exerted by prazosin (0.1 mg/kg) and yohimbine (1 mg/kg) the 5- and 7-OH isomers as well as DPDA can be classified as mixed α1/α2-adrenoceptor agonists, the α1-adrenoceptor-stimulating potency being more pronounced, especially for the 5-OH congener. In addition, a significant contribution of serotonin receptors to the pressor responses to the 8-OH compound was detected. Similarly, α2-adrenoceptors were mainly responsible for the vasoconstriction caused by the 6,7-di-OH isomer, whereas the 5,6-di-OH congener very selectively stimulated this α2-type receptor in the lower dose range and α1-adrenoceptor stimulation predominated at higher doses of this agonist. The 6,7-di-OH compound failed to activate vascular postjunctional β2-adrenoceptors. The results indicate that the α1/α2-adrenoceptor agonist activity depends on the position(s) and the number of hydroxy groups present as well as on the alkyl substitution at the amino function. 2-N,N-Di-n-propylamino-6,7-dihydroxytetralin may be a more suitable α2-adrenoceptor selective agonist than M-7.
Original languageEnglish
Pages (from-to)55-65
Number of pages11
JournalEuropean Journal of Pharmacology
Volume97
Issue number1-2
Publication statusPublished - 20-Nov-1984

    Keywords

  • 2 dimethylamino 5,6 dihydroxytetralin, 2 dipropylamino 5 hydroxytetralin, 2 dipropylamino 5,6 dihydroxytetralin, 2 dipropylamino 6 hydroxytetralin, 2 dipropylamino 6,7 dihydroxytetralin, 2 dipropylamino 7 hydroxytetralin, 2 dipropylamino 8 hydroxytetralin, 3 isopropylamino 1 (7 methyl 4 indanyloxy) 2 butanol, adrenergic receptor stimulating agent, alpha 1 adrenergic receptor, alpha 2 adrenergic receptor, clonidine h 3, methysergide, n,n dipropyldopamine, noradrenalin, phentolamine, pimozide, prazosin, prazosin h 3, radioisotope, reserpine, tyramine, unclassified drug, yohimbine, article, autonomic nervous system, blood pressure, cardiovascular system, central nervous system, nonhuman, pressor response, rat, spinal animal, structure activity relation, vasoconstriction

ID: 14353362