Alpha adrenergic and histaminergic effects of tolazoline like imidazolines

J. Sanders, Duane Miller, P. N. Patil

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

For eliciting contraction of rabbit aorta, the relative potency of agonists in terms of negative log molar ED50 were: oxymetazoline (8.4) > naphazoline (7.95) > phenylephrine (7.31) > tetrahydrozoline (6.5) > tolazoline (5.80). None of the imidazolines, however, produced maximal effects equal to that of phenylephrine. All agonists were directly acting agents. The interactions between oxymetazoline and phentolamine or tolazoline and phentolamine were competitive with pA2 values of 8.1 and 8.0 respectively. Phentolamine with tetrahydrozoline, naphazoline or phenylephrine produced nearly equal K(B) values. Thus, all the agonists and alpha adrenoceptor blockers must act at a common site in rabbit aorta. As expected, the contraction of rabbit aorta produced by an imidazole histamine was competitively antagonized by the histamine1 antagonist, chlorpheniramine (K[B] 7.6 x 10-9 M). The antagonist failed to block the contraction produced by the imidazolines studied. On guinea pig aorta, the relative potency of the agonists varied greatly. On guinea pig atria, tetrahydrozoline and tolazoline produced positive chronotropic effects which were not influenced by reserpine and cocaine treatment, or treatment with a beta adrenoceptor blocker, propranolol. The histamine2 receptor antagonist, metiamide, however, selectively blocked the cardiac effects. It is concluded that oxymetazoline and naphazoline do not activate histamine1 or histamine2 receptors or beta adrenoceptors. Thus, the drugs are highly specific alpha adrenoceptor stimulants. On the other hand, tetrahydrozoline and tolazoline interact with histamine2 receptors with alpha adrenoceptors, but not with histamine1 receptors or with beta adrenoceptors.

Original languageEnglish (US)
Pages (from-to)362-371
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume195
Issue number2
StatePublished - Dec 1 1975
Externally publishedYes

Fingerprint

Tolazoline
Histamine Agents
Imidazolines
Adrenergic Agents
Adrenergic Receptors
Oxymetazoline
Naphazoline
Aorta
Phentolamine
Phenylephrine
Rabbits
Guinea Pigs
Metiamide
Chlorpheniramine
Reserpine
Cocaine
Propranolol
Histamine
tetrahydrozoline
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Alpha adrenergic and histaminergic effects of tolazoline like imidazolines. / Sanders, J.; Miller, Duane; Patil, P. N.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 195, No. 2, 01.12.1975, p. 362-371.

Research output: Contribution to journalArticle

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