[Pharmacodynamic effects of d-nicotine--Comparison with l-nicotine]

The acute toxicity and pharmacological effects of d-nicotine were examined in several species of animals and compared with those of l-nicotine. The LD50s for intravenous administration of d- and l-nicotine were 6.15 and 0.33 mg/kg, respectively. In unanesthetized rhesus monkeys, EEG activity was not influenced by d-nicotine, 64 micrograms/kg, i.v., while the same dose of l-nicotine produced seizure-like waves with some spindles. In rats, d-nicotine increased spontaneous motor activity, and in the experiment under a DRL 20-sec schedule, it increased lever press responding, decreased the number of reinforcements and shortened interresponse time. Similar effects were also observed by administration of l-nicotine at lower doses than for the d-isomer. In anesthetized rats, d-nicotine elevated the blood pressure and increased the heart rate with a potency of about one-eighth that of the l-isomer. Further, tachyphylaxis and cross tachyphylaxis were developed to the blood pressure-raising effect in rats after repeated administration of both isomers. d-Nicotine elicited contraction of isolated rat ileum preparations, but with a potency of about one-tenth that of the l-isomer. Both isomers at the same concentration blocked transmission at the neuromuscular junction in isolated rat phrenic nerve-diaphragm muscle preparations. These results indicate that the pharmacological effects of d-nicotine are qualitatively similar to but quantitatively less potent than those of l-nicotine.