ISSN:
1432-2072
Keywords:
Ptosis
;
Reserpine
;
B-HT 920
;
B-HT 933
;
Clonidine
;
α-Adrenoceptors
;
Methoxamine
;
Phenylephrine
;
Norepinephrine
;
Rat
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The relative potency and selectivity of the α-adrenoceptor agonists clonidine, B-HT 920 [2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-(5,4-d)-azepin], B-HT 933 [2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-(5,4-d)-azepin], norepinephrine, phenylephrine and methoxamine were examined using reserpine-induced ptosis in male NMRI mice. Reserpine (2.5 mg/kg, IP) was administered 4 h before IP injection of the α-adrenoceptor agonists, and for interaction studies, various doses of yohimbine or prazosin were injected IP, 15 min before injection of the α-adrenoceptor agonists (in doses equivalent to their ED50 values). All α-adrenoceptor agonists produced dose-related reversal of ptosis with effects that were maximal about 15–30 min after injection. Comparison of ED50 values for agents with predominantly α 2-agonist activity indicated that clonidine was about 24 times more potent than B-HT 920 and about 580 times more potent than B-HT 933 in reversing ptosis. For substances with pronounced, or predominant, α 1-agonist activity, phenylephrine was about 1.5 times more potent than methoxamine and about 3 times more potent than norepinephrine in reversing ptosis. The ratio of equi-effective doses of B-HT 920/methoxamine (α 1/α 2 importance) in reversing reserpine-induced ptosis was about 2.0, indicating that α 1-adrenoceptors played a predominant role. The α 1-antagonist prazosin antagonized the effects of norepinephrine, phenylephrine, methoxamine and clonidine with similar potency, but was much less effective against the more selective α 2-agonists B-HT 920 and B-HT 933. Yohimbine, on the other hand, was a more potent antagonist of the effects of predominantly α 2-agonists than of predominantly α 1-agonists. On the basis of these results, methoxamine appears to be the most selective α 1-agonist, and B-HT 920 and B-HT 933 exhibit the greatest selectivity for interaction with α 2-adrenoceptors. Although reversal of reserpine-induced ptosis is not selective for α 1- or α 2-adrenoceptors agonists in the mouse, this test might be useful for comparing the relative potencies of α-adrenoceptor agonists as well as for providing an indication of their relative degree of selectivity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00436162
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