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Biomedical subjects

R D Waigh

Publications and source records attributed to R D Waigh.

26 records · Page 2Linked to original sources
PubMed1983

Synthesis and analgesic properties of two leucine-enkephalin analogues containing a conformationally restrained N-terminal tyrosine residue.

Two analogues of Leu-enkephalin, in which the terminal tyrosine-1 residue has been replaced by a conformationally restrained tyrosine analogue, have been synthesized by classical solution methods, and their opiate agonist potencies on electrically stimulated guinea pig ileum and mouse vas deferens preparations were determined in comparison with Leu-enkephalin. The restriction in the degree of freedom of the tyrosine moiety in [(2-amino-6-hydroxy-2-tetralinyl)carbonyl]glycylglycylphenylalanylleucine methyl ester (3e) leads to a 7 to 8 times higher agonist activity at the mu-receptor subtype in guinea pig ileum when compared to Leu-enkephalin, and an almost 30-fold decrease in potency, vs. Leu-enkephalin, on mouse vas deferens preparation. [(2-Amino-5-hydroxy-2-indanyl)carbonyl]-glycylglycylphenylalanylleucine methyl ester (2e) was inactive in the above tests. These results demonstrate the differential effect of restricting conformational flexibility on receptor recognition. Neither analogue had any analgesic properties when evaluated by the hot-plate test in mice after sc and icv administration.

Animals↗
PubMed1983

Atracurium: conception and inception.

The rationale underlying the design of atracurium, a bis-quaternary ammonium neuromuscular blocking agent which incorporates the Hofmann elimination as a novel biodegradation pathway, is described. Destruction in vivo, of the bis-quaternary structure essential for neuromuscular blocking activity, by the combination of Hofmann elimination and a parallel ester hydrolysis leads to innocuous breakdown products that are without neuromuscular or cardiovascular effects and to a time-course of action which is unaffected by the level of plasma esterase activity, renal or hepatic function.

Animals↗
PubMed1981

A preliminary assessment of atracurium, a new competitive neuromuscular blocking agent.

Atracurium besylate, 2,2'-(3,11-dioxo-4,10-dioxatridecylene)-bis-[6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl 1,2,3,4-tetrahydroisoquinolinium] dibenzenesulphonate is a potent non-depolarising (competitive) neuromuscular blocking agent in the cat, monkey, dog and anaesthetized man. In man, it caused complete paralysis of the tetanic response of the adductor pollicis muscles at doses of 0.2 mg/kg. Blockade was of medium duration with rapid spontaneous recovery, and was readily reversed by neostigmine. The electrocardiogram, heart rate, arterial blood pressure and central venous pressure were virtually unchanged following doses of 0.2-0.4 mg/kg. Intubation was readily accomplished in 1.5-2 min after administration of 0.25-0.3 mg/kg.

Animals↗
PubMed1979

Actions of two dopamine derivatives at adreno- and cholinoceptors.

Salsolinol (1)and 6,7-dihydroxy-1,1-dimethyl-1,2,3,4-tetrahydroisoquinoline hydrobromide (2) were synthesized and their effects at adreno- and cholinoceptors investigated both in vivo and in vitro. Both 1 and 2 produced agonist effects at cholinoceptors and alpha- and beta-adrenoceptors. Neuromuscular blocking actions were evident in vitro. Compound 2 exhibited anticholinesterase properties both in vivo and in vitro. These results indicate that dopamine derivatives of this type exhibit not only sympathomimetic activity but also complex actions at cholinoceptors.

Animals↗