Activity Of Central Noradrenergic Neurons Research Articles

Abnormal central noradrenergic neuronal activity in patients with diabetes mellitus

Abnormal central noradrenergic neuronal activity in patients with diabetes mellitus

Clonidine in mania

AbstractHyperactivity of central noradrenergic neurotransmission has been implicated in the pathophysiology of mania. This theory suggests that clonidine, an antihypertensive medication that decreases the activity of central noradrenergic neurons by presynaptic inhibitory effect, has antimanic properties. We administered clonidine orally in a dosage of 17 μg/kg/day to 11 hypomanic or manic patients. Biegel‐Murphy Manic‐State Rating Scale scores were significantly decreased compared to pretreatment scores at day 10 and day 25 of clonidine treatment (P < .001). Sedation, hypotension, and depression were noted but were not limiting. Though the results of this study are only preliminary, clonidine alone or in combination with lithium may have advantages over neuroleptics in the acute stages of mania, including avoidance of extrapyramidal side effects and risk of tardive dyskinesia.

Central norepinephrine metabolism during alcohol intoxication in addicts and healthy volunteers.

The concentrations of the major norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), in lumbar cerebrospinal fluid of alcoholic patients were markedly elevated during intoxication and successively declined during 1 and 3 weeks of abstinence. During intoxication the MOPEG concentration in cerebrospinal fluid showed a statistically significant correlation with the blood alcohol concentration. In healthy volunteers who received 80 grams of ethanol, the MOPEG concentration in cerebrospinal fluid increased significantly. Healthy subjects sampled during intoxication had significantly higher concentrations of MOPEG in the cerebrospinal fluid than did subjects sampled after the end of intoxication. The results indicate that alcohol administration markedly stimulates norepinephrine metabolism in the central nervous system in human subjects possibly by increasing unit impulse activity of central noradrenergic neurons.

Antagonism by mianserin and classical α-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine

Antagonism of pressor responses to sympathetic outflow stimulation and α-adrenoceptor agonists in pithed spontaneously hypertensive rats was used to estimate postsynaptic α-adrenoceptor blocking activity of mianserin, phentolamine, phenoxybenzamine, piperoxan and yohimbine. Estimation of presynaptic α-adrenoceptor blocking activity of these drugs was obtained by studying their ability to antagonize clonidine-induced suppression of positive chronotropic responses to sympathetic outflow stimulation. In this manner, evidence was obtained that mianserin causes selective presynaptic α-adrenoceptor blockade. Mianserin, piperoxan and yohimbine antagonized clonidine-induced avoidance blockade or hypotension in spontaneously hypertensive rats, but methysergide, phenoxybenzamine and phentolamine were ineffective. These results suggest that mianserin may antagonize the central effects of clonidine by blockade of noradrenergic presynaptic or autoreceptors and possibly explain the antidepressant effect of mianserin as due to indirect activation of central noradrenergic neurons.