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The effects of N‐(cyclopropylmethyl)‐19‐isopentyl‐nororvinol (M320), a potent agonist at k ‐ and μ‐ opiate receptors, on urine excretion of rats
Author(s) -
Abrahams J.M.,
Boura A.L.A.,
Evans R.G.,
Johnston C.I.,
Olley J.E.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11180.x
Subject(s) - endocrinology , medicine , chemistry , vasopressin , excretion , urine , diuresis , agonist , urine osmolality , receptor , kidney
1 The effects of N‐(cyclopropylmethyl)‐19‐isopentylnororvinol hydrochloride (M320) on urine excretion by rats were investigated. Further studies, using rabbit isolated vas deferens, investigated its interactions with k ‐opiate receptors. 2 The output of urine for a 2 h period after M320, administered subcutaneously to normally hydrated Long Evans rats, showed a bell‐shaped dose‐response relationship, the maximum effect occurring after 10 μg kg −1 . Urinary retention contributed to but did not fully account for the weaker diuresis after high doses. Attenuation of the ascending portion of the dose‐response curve to M320 occurred after 1 and 10 mg kg −1 but not 0.1 mg kg −1 of naltrexone intraperitoneally. 3 M320 in low doses (3–10 μg kg −1 ) caused a small but significant increase in sodium excretion. M320 (30 μg kg −1 ) reduced both sodium and potassium excretion. 4 M320 (10 μg kg −1 s.c.) did not increase the volume of urine voided in 2 h by Brattleboro rats showing diabetes insipidus, even when urine excretion was reduced to normal by 1 week of vasopressin replacement. 5 The volume of urine voided in 4 h by Brattleboro rats was progressively reduced to zero by M320 (10–100 μg kg −1 s.c). Urinary retention contributed to but did not account for this reduction. 6 Plasma levels of immunoreactive arginine vasopressin (ir‐AVP) were reduced in both normal and dehydrated Long Evans rats after doses greater than 1 μg kg −1 M320 s.c. 7 In vitro , M320 caused persistent inhibition of twitches of the electrically stimulated rabbit vas deferens (IC 50 1.7 nM). 8 These data suggest that M320 has potent opioid agonist activity at k ‐receptors and at higher concentrations stimulates μ‐ receptors. In the rat, its activity on k ‐receptors is associated with diuresis and suppression of plasma vasopressin levels. The antidiuresis seen after high doses may be due to its activity on μ‐receptors, possibly at a central site.