A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse.

Synaptic events in sympathetic ganglia.

The action of 5-hydroxytryptamine on single neurones of the rabbit superior cervical ganglion

The effects of 5-hydroxytryptamine (5-HT) and related indole derivatives injected as i.a. bolus injections in a large dose range were studied in the cat superior cervical ganglion (SCG) by recording ganglionic and postganglionic electrical activity. 5-HT had two independent and opposite actions: a long-lasting inhibition of ganglionic transmission occurred already with extremely low doses and increased up to highest ones: both pre-and postsynaptic sites of action seem to be involved. In a medium and high dose range, the inhibitory effect was temporarily masked by a short-lasting stimulation and a depolarisation which was small when compared with that produced by nicotinic agents. The depolarization triggered a secondary hyperpolarization. The stimulant, but not the inhibitory action was very prone to tachyphylaxis.

The effects of 5-hydroxytryptamine and some related compounds on the cat superior cervical ganglion in situ.

Five drugs [(−)- and (+)-nicotine, (−)-lobeline, (−)-anabasine and (−)-cytisine] were infused IV into the urethane-pentobarbital anesthetized rat. Changes in heart rate, blood pressure, respiratory rate, minute and tidal volume, which appeared to be largely centrally mediated, were studied. Each of these compounds produced different pharmacologic profiles. The nature of these dissimilarities is not readily explained on the basis of pharmacokinetic considerations suggesting that the drugs have different mechanisms of action. Binding data obtained with these compounds using the rat brain P2 preparation also show differences. (−)-Lobeline and (−)-anabasine, like the nicotinic antagonists mecamylamine and hexamethonium, bind predominantly to low affinity sites with KDs in the micromolar range whereas (−)-cytisine binds only to a single high affinity site with a KD in the nanomolar range. Further, the binding patterns of these drugs are different from (−)- and (+)-nicotine which bind to both high and low affinity sites but differ from each other in binding characteristics. Thus the binding data are consistent with the pharmacologic data in suggesting that the drugs have different modes of action and support the concept that the low affinity site has an important role in the central nervous system action of these compounds.

Volle Rl

Papers

A comparison of the ganglionic stimulating and blocking properties of some nicotinic drugs.