G. Victor Rossi

isolated lung strips of guinea pigs: Responses to β-adrenergic agonists and antagonists☆

Isolated lung strips of guinea pigs were examined as an in vitro model for assessing the direct effect of beta-adrenergic drugs at the level of peripheral airways. Changes in intrinsic tone of thin strips of lung parenchyma were measured with an isometric force transducer. Isoproterenol, a nonselective beta-adrenergic agonist, and several beta-adrenergic agonists, soterenol, salbutamol, metaproterenol and ritodrine elicited a dose-related relaxation of lung strip. Responses to isoproterenol were antagonized by propranolol and the selective beta blocking agents butoxamine (beta2) and practolol (beta1). These results were compared to data obtained with the same compounds on isolated guinea pig atria. All agonists except ritodrine were full agonists in the lung strip whereas isoproterenol and metaproterenol were the only full agonists in the atrial preparation. In the atria, practolol was a more effective blocker of isoproterenol responses than butoxamine, and the reverse was true for the lung strip.

Evidence that renal vasodilation by dopamine in dogs does not involve release of prostaglandin.

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Metabolism of dopa-14C in the normal and α-methyldopa-treated mouse

Abstract Intraperitoneally injected dl -3, 4-dihydroxyphenylalanine (dopa)-α- 14 C was rapidly metabolized in the intact mouse; the biological half-life was approximately 15 min. Decar☐ylation constituted an important but not the only route of metabolism. One hour after the administration of dopa- 14 C the following labeled catechols were found in whole mouse homogenates (concentrations expressed as a percentage of total recovered radioactivity): dopa (17.3%), dopamine (13.8%), norepinephrine (1.2%), epinephrine (0.5%), 3,4-dihydroxyphenylacetic acid (dopac) (0.8%). α-Methyldopa, injected intraperitoneally in a dose of 3.12 mg/kg, inhibited the decar☐ylation in vivo of dopa- 14 C. Larger doses resulted in progressively greater inhibition; maximal response was obtained with 50 mg/kg. In mice given α-methyldopa (25 mg/kg) 30 min prior to dopa- 14 C and sacrificed 1 hr later, the dopa level was increased (30.6%), and the dopamine level was reduced (3.8%). The duration in vivo of the decar☐ylase inhibitory activity of α-methyldopa in the mouse was 8 to 16 hr.

Tremor production by intracaudate injections of morphine

Pronounced resting tremor was produced in unanesthetized cats by injecting morphine (25-110 mug) into the caudate nucleus. The effects of morphine were antagonized by intracaudate (i.c.) injections of nalorphine (81-263 mug). Tremor activity was also inhibited by i.c. injections of dopamine (61-145 mug), Ca2+ (24-40 mug), scopolamine (88-121 mug) and hemicholinium-3 (HC-3; 73-129 mug) while serotonin (125 mug) was ineffective. Tremor inhibition by HC-3 was reversed by i.c. doses of acetylcholine (15-30 mug) which were subthreshold for tremor production in the absence of morphine. Morphine (55-110 mug) further increased the intensity of ongoing tremor activity induced by physostigmine (111 mug i.c.) I.c. injections of nalorphine antagonized the motor effects of morphine without affecting physostigmime tremor. Tremor production by morphine is attributed to a reduction in dopamine function which allows cholinergic activity in the caudate nucleus to predominate.

Interactions of chlorpheniramine ethanol combinations: Acute toxicity and antihistaminic activity

Abstract Significant toxicologic and pharmacologic interactions occurred between chlorpheniramine maleate and 25% v v ethanol at several dosage combinations. Conditions of both independence and antagonism of acute toxicity were observed in LD50 determinations of chlorpheniramine-ethanol combinations in mice, and confirmed expected results based on the toxicologic pattern of the agents when administered singly. Enhancement of the antihistaminic action of chlorpheniramine by ethanol was demonstrated during histamine-aerosol challenge studies in guinea pigs.

Doxepin and imipramine: Effect on catecholamine inhibition of ganglionic transmission

Abstract Doxepin (DOX) and imipramine (IM) administered by close intra-arterial injection (25, 40 and 60 μg/kg) potentiated the inhibitory effect of norepinephrine (NE) on electrically-evoked postganglionic potentials in the superior cervical ganglion of the cat. Dose-response relationships indicated no significant difference between DOX and IM with regard to their effect on NE activity. Potentiation of dopamine (DA)-induced suppression of ganglionic transmission by DOX and IM (25, 40 and 60 μg/kg) was not as pronounced as the potentiation of NE activity by these two antidepressants. Significant potentiation of DA was evident only at the 40 and 60 μg/kg dose levels of DOX and IM. Dose-response relationships indicated that potentiation of DA by DOX was significantly greater than that produced by IM.

Modification of certain vascular responses to dopamine by morphine

Abstract Alteration by morphine of two specific vascular responses to dopamine, systemic hypotension in cats and renal vasodilation in dogs, were characterized in α-adrenergically blocked (phenoxybenzamine) anesthetized animals. Morphine sulfate (15–30 mg/kg, i.v.) converted the vasodepressor response to dopamine (50–100 μg/kg, i.v.) to a pressor response in intact cats, whereas in spinal cats dopamine-induced vasodepression was not significantly altered by morphine (15–60 mg/kg, i.v.). Haloperidol, a putative peripheral dopaminergic receptor antagonist, briefly but significantly attenuated the hypotensive response to dopamine in spinal cats. Canine renal vasodilator responses to intrarenal arterial dopamine (0.09–96 μg) were significantly reduced after morphine (2–6 mg/kg, i.a.). Morphine produced a non-parallel shift in the dopamine dose-response curve, whereas a parallel shift was obtained when haloperidol was used as the antagonist in the canine renal test system. These results do not support the concept that morphine may be a competitive antagonist of dopamine at peripheral dopaminergic receptors in these species.