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At least 19 recordsLinked to original sources

PubMed1977

Interaction between yohimbine alkaloids and amphetamine in mice.

The toxicity (LD50) of the isomers yohimbine, beta-yohimbine, and corynanthine was determined in mice. The LD50 of amphetamine in the presence of a constant dose of a yohimbine isomer and that of the isomer in the presence of a constant dose of amphetamine were determined in aggregated mice. Isobolograms were constructed from these data and used to evaluate the interaction of the yohimbine alkaloids and amphetamine. Beta-yohimbine was found to be approximately twice as toxic as yohimbine and corynanthine about one fifth as toxic. There was a mutual potentiation between the toxicities of yohimbine and amphetamine. Potentiation of the toxicity of amphetamine occurred with beta-yohimbine but the effect was not as marked as with yohimbine. In contrast, corynanthine antagonized the toxicity of amphetamine. The interaction between yohimbine and amphetamine is unlikely to be due to noradrenergic mechanisms but could conceivably involve serotonergic or dopaminergic mechanisms.

Animals↗

PubMed1978

Yohimbine blockade of ionic channels in myocardial cells.

The effects of yohimbine, an alkaloid shown to have local anesthetic properties on nerve, were determined in isolated perfused chick embryonic (19--21-day-old) hearts. Effects on the fast Na+ channels were studied in hearts perfused with normal Ringer solution by using the maximal upstroke velocity (+Vmax) as an index of the inward current flowing during the rising phase of the normal action potential. Yohimbine (10(-5)--10(-4) M) depressed +Vmax and overshoot and prolonged the action potential. At 5 x 10(-4) M, yohimbine completely blocked the fast Na+ channels, since this dose abolished the action potential when Mn2+ (2 mM) was present to eliminate the slow Ca2+ current. Effects on the slow channels were studied in hearts in which the fast Na+ channels were voltage-inactivated by partial depolarization to about--40 mV with an elevated (25 mM) K+-Ringer solution or blocked by tetrodotoxin (TTX), resulting in loss of excitability. Isoproterenol (10(-6) M) restored excitability by inducing a slowly rising overshooting electrical response (the "slow response") that was accompanied by contractions. At low concentrations (10(-5)--10(-4) M), yohimbine enhanced the isoproterenol-induced slow response; yohimbine induced the slow response in the absence of isoproterenol, even in the presence of a beta-adrenergic blocker. In contrast, at high concentrations (10(-3) M), yohimbine markedly depressed or blocked the slow response. Consistent with this dual action, yohimbine exerted a small positive inotropic action at low doses in hearts perfused with normal Ringer solution and exerted a considerable negative inotropic action at high doses, causing complete blockade of the contractions within 20 min. Cultured reaggregated cells obtained from chick embryo (15--17 day-old) ventricles showed a similar response to yohimbine in that both the normal action potentials and the slow responses were abolished. It is concluded that yohimbine exerts a local anesthetic-like action on myocardial cells, since both fast and slow channels were blocked, but the fast channels were more sensitive to yohimbine.

Action Potentials↗

PubMed1979

Yohimbine blocks lateral hypothalamus-mediated behaviors.

There exist behavioral and physiological similarities between rats injected with yohimbine and those with lesions of the lateral hypothalamus. The present study sought to determine if behaviors mediated by the lateral hypothalamus would be significantly altered by yohimbine. Deficits in performance of an active avoidance task have been observed after lateral hypothalamic lesions. Likewise, in the present experiment, yohimbine significantly reduced the ability of trained rats to perform in a similar paradigm. Systemic injections of yohimbine caused decrements in lateral hypothalamic self-stimulation behaviors as well as in locomotor activity produced by lateral hypothalamic stimulation. Similar behaviors mediated by the substantia nigra were relatively unaltered by yohimbine. A final experiment revealed that yohimbine reduces the enhanced glucose utilization normally observed at the lateral hypothalamus during electrical stimulation. These data support the view that the lateral hypothalamus may be an important target of yohimbine's CNS actions.

Animals↗

PubMed1975

The effect of yohimbine on the turnover of brain catecholamines and serotonin.

Yohimbine moderately increased the depletion of brain dopamine (DA) after alpha-methyl-p-tyrosine (AMT) only when the two drugs were given at the same time; the baseline concentration of brain homovanillic acid (HVA) and its accumulation after probenecid were strongly increased by yohimbine. Yohimbine markedly decreased the concentration of brain noradrenaline (NA), both when given alone and before or at the same time as AMT; when it was given at an increasing interval after AMT, the effect became progressively smaller. The baseline concentration of brain 3-methyoxy-4-hydroxyphenylethyleneglycol sulphate and its accumulation after probenecid were increased by yohimbine; this effect was not as marked as that on HVA and was proportional to the quantity of NA depleted in the Amt method. The accumulation of brain k-hydroxyindoleacetic acid after probenecid was decreased by yohimbine pretreatment.

Animals↗

PubMed1978

Effects of yohimbine on squid axons.

Yohimbine, an indolealkylamine alkaloid, reduces the amplitude of the sodium current in the squid giant axon. For doses that reduce sodium current amplitude by up to 50%, there is no significant change in the kinetics or in any of the voltage-dependent parameters associated with sodium channels. The effective equilibrium constant for yohimbine binding to the sodium channel is 3 x 10(-4) M. Repetitive depolarizing pulses increase the inhibition of squid axon sodium current by yohimbine. This use-dependent inhibition is enhanced by increasing the concentration of yohimbine, by increasing the frequency of pulsing, and by increasing the magnitude or the duration of depolarization. It is reduced by hyperpolarizing prepulses. This behavior can be explained by a model wherein yohimbine binds more readily to open sodium channels than to closed sodium channels and wherein the Hodgkin-Huxley kinetic parameters are modified by the binding of the drug. This type of model may also explain the tonic and use-dependent inhibition previously described by others for local anesthetics.

Action Potentials↗

PubMed1975

The role of the central nervous system in the cardiovascular responses to yohimbine.

Yohimbine injected intravenously or intracerebroventricularly in conscious dogs produced behavioural excitation accompanied by a rise in blood pressure and heart rate. The cardiovascular effects were reduced or abolished by hexamethonium, phenoxybenzamine and reserpine. In conscious cats intravenously administered yohimbine was depressor but intracerebroventricular administration in these animals caused a rise in blood pressure accompanied by behavioural depression. In anaesthetized or decerebrate cats yohimbine was always depressor. Yohimbine injected intracerebroventricularly produced a rise in blood pressure and heart rate in both conscious and anaesthetized rats. When administered intravenously to these animals there was a fall in blood pressure. It was concluded that the pressor action of yohimbine in conscious dogs was central in origin via the sympathetic nervous system. The different pattern of cardiovascular responses in the dog, cat and rat may be related to differences in the balance between medullary effects and effects on higher brain centres of the three species.

Adrenergic alpha-Antagonists↗

PubMed1978

Interaction between batrachotoxin and yohimbine.

The neurotoxins, batrachotoxin and veratridine, are specific activators of sodium channels and cause an increase in the rate of 22Na uptake in neuroblastoma cells. Yohimbine, an indolakylamine alkaloid, inhibits this batrachotoxin-induced 22Na uptake. The dose-response curve of yohimbine suggest that the inhibitor acts reversibly on a single class of binding sites with dissociation constant of 3--4 x 10(-5) M. The dissociation constant is not affected by depolarization from--41 to 0 mV. Kinetic and equilibrium experiments indicate that yohimbine is a competitive inhibitor of the action of batrachotoxin. These results support the conclusion that yohimbine inhibitis the sodium flux by acting on the channel gating mechanism rather than by occluding the channels.

Batrachotoxins↗

PubMed1992

Effects of yohimbine on heart rate variability in panic disorder patients and normal controls: a study of power spectral analysis of heart rate.

We studied the effects of yohimbine on heart rate (HR) variability in 13 normal controls and 13 patients with panic disorder. Yohimbine produced a significant increase in SD of HR in standing posture in both patients (p = 0.01) and normal controls (p = 0.025). Panic disorder patients had a significant increase in standing absolute midfrequency (MF) power (0.07-0.15 Hz) after administration of yohimbine (p = 0.002). The ratio of post- to preyohimbine standing MF power (0.07-0.15 Hz) during standing was significantly higher in patients as compared with controls (2.3 +/- 1.08 vs. 1.33 +/- 0.38; p = 0.01), which suggests an increased responsivity of panic disorder patients to the adrenergic effects of yohimbine.

Adult↗

PubMed1978

Yohimbine-induced stimulus control in the rat.

Rats were first trained in a 2-lever operant test chamber using a fixed ratio 10 schedule of water reinforcement. Discrimination training was then begun. In sessions following the injection (i.p.) of yohimbine . HC1 (3 mg/kg), responses on 1 of the 2 levers were reinforced. In sessions following the injection of saline, responses on the remaining lever were reinforced. The distribution of responses between the 2 levers prior to reinforcement provided an index of discrimination. The criterion for stimulus control was set at 80% correct responses in each of five consecutive sessions. In a group of six rats, criterion performance was begun after a mean of 33 sessions. Cross tests were conducted in yohimbine-trained subjects with d-amphetamine, harmaline, and LSD. Each test drug yielded intermediate results, i.e., response distribution was significantly different from both the yohimbine and the saline training conditions. No significant antagonism of yohimbine-induced stimulus control was achieved with BC-105, phentolamine, or butaclamol, purported antagonists at serotonergic, alpha-adrenergic, and dopaminergic receptor sites, respectively.

Animals↗

PubMed1975

Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine.

Strips of the rabbit main pulmonary artery were preincubated with 3H-noradrenaline. 3 X 10(-8) -- 10(6) M yohimbine enhanced the overflow of tritium and the smooth muscle contraction induced by transmural sympathetic nerve stimulation. The increase of the stimulation-evoked overflow of tritium was prevented by a high concentration of oxymetazoline. The results indicate that yohimbine is more potent in blocking the presynaptic than the postsynaptic alpha-adrenoceptors of the artery.

Animals↗

PubMed1977

Effect of clonidine and chlorpromazine on centrally evoked electrodermal responses and their interaction with yohimbine.

Both clonidine and chlorpromazine reduced the amplitude of electrodermal responses (EDR) evoked by stimulation of the hypothalamus at a constant submaximal frequency (10-16 Hz). The ED50 for clonidine was approximately 5 mug/kg and that for chlorpromazine was about 1 mg/kg. Yohimbine pretreatment (0.5 mg/kg, i.v.) antagonized the effects of clonidine but did not alter the effectiveness of clorpromazine in inhibiting these responses. Yohimbine alone was without effect on these sympathetic-cholinergic responses. These results suggest that clonidine and chlorpromazine deress central sympathetic reactivity by different mechanisms.

Animals↗

PubMed1978

alpha-Adrenergic modulation of hypothalamic self-stimulation: effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine.

The alpha-adrenoceptor agonist clonidine (12.5--50.0 microgram/kg) produced a dose-dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic alpha-adrenoceptor antagonist phenoxybenzamine (0.2-0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inhibitory effects of clonidine. The fact that the concurrent escape behavior to the intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5--2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity, Dexamphetamine (0.25--0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. These data support the concept that the alpha-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidine on self-stimulation reward represent an agonist effect on presynaptic alpha-adrenoceptors.

Animals↗

PubMed1978

Pharmacological and biochemical properties of isomeric yohimbine alkaloids.

The stereochemical and pharmacological properties of yohimbine and some of its isomers are briefly reviewed. Several pharmacological and physical properties of a selection of the isomers have been determined with a view to elucidating which might be important in the elaboration of the known behavioral effects produced by them. Activity is not dependent upon lipid solubility or on the ease of access to the central nervous system. The isomers are weak inhibitors of rat-brain acetylcholinesterase and weak antagonists at muscarinic cholinergic receptors. In the rat brain in vitro they do not possess significant monoamine oxidase-inhibiting properties nor do they inhibit the uptake of serotonin. They are relatively potent antagonists of 5HT on the rat isolated fundus preparation and their potency in this preparation may be related to their ability to produce behavioral and cardiovascular effects in man and dogs.

Animals↗

PubMed1976