TL-350, an ergoline derivative with dopamine receptor agonist properties.

Abstract

Intravenous and intraduodenal injection of a new ergoline derivative, TL-350, produced dose-dependent inhibition of heart rate increase produced by cardioaccelerator nerve stimulation in anesthetized cats. ID50 values of TL-350 were 0.019 and 0.047 mumol/kg after i.v. and intraduodenal injection, respectively. This inhibition was reversed by either sulpiride (0.15 mumol/kg i.v.) or haloperidol (0.13 mumol/kg i.v.) but not by yohimbine (0.14 mumol/kg i.v.). TL-350 did not change isoproterenol-induced tachycardia and hypotensive responses. TL-350 caused dose-dependent decrease of arterial blood pressure and heart rate in anesthetized cats. Haloperidol (0.13 mumol/kg i.v.) prevented the hypotensive and bradycardic effects of the compound. TL-350 also produced concentration-dependent inhibition of heart rate responses to transmural stimulation of isolated cat right atria. IC50 value was 0.026 microM. Dopaminergic antagonists, haloperidol and sulpiride, antagonized the inhibitory effect of TL-350 in in vitro experiments. TL-350 did not stimulate presynaptic alpha-2 adrenergic receptors in rat vas deferens and guinea-pig ileum. TL-350 induced rotation for 3 hr in rats with unilateral denervated caudate nucleus. The compound was 0.5 as potent as apomorphine. In [3H]dopamine binding assays using rat caudate tissue, TL-350 had approximately the same activity as apomorphine in displacing the radioligand. It was concluded that TL-350 is a selective dopamine receptor agonist without possessing alpha and beta adrenergic receptor stimulating activity.

• Authors: M Ilhan, J P Long, R Bhatnagar, J Flynn, J G Cannon, T Lee
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 231 Issue 1 Pg. 56-60 (Oct 1984) ISSN: 0022-3565 [Print] United States
• PMID: 6548524 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ergolines
• Indoles
• Receptors, Dopamine
• TL 350
• Apomorphine

Topics

• Animals
• Apomorphine (pharmacology)
• Blood Pressure (drug effects)
• Cats
• Dose-Response Relationship, Drug
• Electric Stimulation
• Ergolines (pharmacology)
• Female
• Guinea Pigs
• Heart Rate (drug effects)
• Ileum (drug effects)
• In Vitro Techniques
• Indoles (pharmacology)
• Male
• Rats
• Receptors, Dopamine (drug effects)
• Trachea (drug effects)
• Vas Deferens (drug effects)