Local Anesthetic Activity of β-Adrenergic Blocking Drugs in the Crayfish Giant Axon, with Reference to Calcium Ion

Abstract

Abstract-The secretory responses to seven dopamine amino acid conjugated derivatives were compared with those to dopamine, using blood-perfused canine pancreas pre parations. Each of these dopamine derivatives produced a dose dependent increase in the secretion of pancreatic juice. The rank order of the secretory responses and relative potency (dopamine =1) was: N-Ileu-dopamine (0.4)>N-Ala-Glu-dopamineThe duration of action of doses of the derivatives which produced approximately equal secretory responses was about 1.22.7 times longer than that of dopamine. Dopamine and N-Ileu-dopamine which has the most potent secretagogue property among seven dopamine derivatives produced a secretin-like secretion of the pancreatic juice con taining a high concentration of bicarbonate but had little effect on protein output with lower amylase activity.Dopamine is a precursor of noradrenaline and has characteristics which form other catecholamines, on systemic blood pressure (1, 2), in the renal or mesenteric vascular bed (1, 3) and in the coronary circulation (4). These effects of dopamine may be the result of actions on specific dopamine receptors (5).It has been reported that dopamine produced an increase in the secretion of pancreatic juice in dogs but that noradrenaline had no effect on pancreatic secretion (6). As the secretagogue effect of dopamine was antagonized by haloperidol it was suggested that there were specific dopamine receptors in the dog pancreas (7).Recently, several dopamine derivatives were synthesized and were found to protect the molecule at its metabolically vulnerable sites (8-12). In the present study, secretory re sponses to dopamine and seven amino acid conjugated derivatives of dopamine were com pared, using the blood-perfused dog pancreas preparation.Moreover, we attempted to determine among the seven dopamine derivatives, compositions of the pancreatic juice induced by secretin, dopamine and N-lieu-dopamine which had the most potent secre tagogue properties. MATERIALS AND METHODSTen mongrel dogs of either sex, weighing from 44 to 17 kg, were fasted for 24 hr and anaesthetized with sodium pentobarbital (30 mg/kg, i.v.). During the experimental pro

Paradoxical effect of noradrenaline-mediated neurotransmission in the antinociceptive phenomenon that accompanies tonic–clonic seizures: Role of locus coeruleus neurons and α2- and β-noradrenergic receptors

“…Interestingly, some β-noradrenergic receptor antagonists have been shown to have local anesthetic effects [55][56][57]. Together with its classic nonselective β-noradrenergic receptor antagonist effect, it has been accepted that propranolol inhibits high-voltage activated Ca 2+ currents and a low-voltage activated Ca 2+ current [58,59] at low concentrations and moderately suppresses potassium currents at high concentrations [60].…”

Chemical modulation of bioactive compounds via oligopeptide or amino acid conjugation

“…However, due to its hydrophilicity, dopamine cannot penetrate the blood‐brain barrier. Several dopamine conjugates were synthesized with amino acids or peptides including glycine, proline, alanine, leucine, phenylalanine, and isoleucine, to alter the partition coefficient of dopamine . Dopamine‐amino acid conjugates showed a seven to ten folds increase in their partition coefficient in n ‐octanol and phosphate buffer saline (pH 7.4).…”