General Pharmacological Actions

Ibogaine produces complex effects on locomotor activity in rodents. A dose of 20 mg/kg (i.p.) slightly increased locomotor activity in mice (75), 

Rats injected with doses of 20-60 mg/kg of ibogaine displayed slower response times on sensory and sensory-motor tests and were also impaired in performing specific motor reflexes at doses of 40-60 mg/kg. Furthermore, these rats exhibited a marked reduction in locomotor activity as well as in emotionality at doses ranging from 10-40 mg/kg. At higher doses ( 40 mg/kg), rats appeared virtually inactive (78). In other studies, at doses above 25 mg/kg, ibogaine produced ataxia, splayed hind limbs, outstretched forelimbs, Straub tail, and hyperexcitability (79). 

Ibogaine has been found to affect the motor stimulant properties of amphetamine, cocaine, and morphine in rodents (hyperlocomotion induced by these drugs is believed to reflect their psychotomimetic qualities in man). Although the results of these studies are not uniform, in general, it has been found that in female rats this alkaloid potentiates the locomotor response to amphetamine and cocaine, whereas opposite effects were reported in male rats and mice. 

Sershen et al. (81) found that ibogaine (40 mg/kg, i.p., 2 or 18 h before amphetamine) enhanced amphetamine (1 mg/kg)-induced hypermotility in female rats. In other studies, an amphetamine-induced increase in locomotor activity was potentiated in female rats pretreated with ibogaine (40 mg/ kg, i.p.) 19 h earlier (82). Cocaine-induced hypermotility in female rats was 

O-Desmethylibogaine (10-40 mg/kg) also inhibited morphine-induced hyperlocomotion in female rats. However, in male rats, the dose of 10 mg/ kg potentiated and 40 mg/kg inhibited morphine-induced hyperlocomotion (66,89). 

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The general pharmacological actions of adrenomimet-ics are described in detail in Chapter 10. The principal pharmacological effects that may be observed in humans treated for bronchospasm are bronchodilation, tachycardia, anxiety, and tremor. Stimulating Pz-adreno-ceptors produces all of these effects either directly or indirectly. 

Hardman, H.F., Domino, E.F., and Seevers, M.H. General pharmacological actions of some synthetic tetrahydrocannabinol derivatives. Pharmacol. Rev. 23 295-315, 1971. 

Tile general pharmacological action of codeine is similar 10 that of morphine, but as indicated above, it does not possess the same analgesic potency. Studies indicate that a dose uf. fO to 120 mg of ctxleinc is considerably less efficient uninterally than 10 mg of morphine, and the usual side effects of morphine—respiratory depression, constipation, nausea, and such—occur. Codeine is less effective orally lhan pareiitemlly, and Houde and Wallenstein stated that a do.se of. 52 mg of codeine is about as effective as 650 mg nf aspirin in relieving terminal cancer pain. Combinations... 

Animal pharmacology a summsiry along with specific and general pharmacological actions and phzirmacokinetic data. 

These general results have entailed much detailed chemical and pharmacological work on the influence of structural changes on particular items in the pharmacological action of morphine, e.g., its effect on respiration. ... 

Pharmacological Action. According to Curci, oxyacanthine in doses of 01 to 0-2 gm. produces in rabbits quick and laboured respiration, muscular tremors, clonic convulsions and cessation of respiration before the heart stops. Raymond-Hamet states that oxyacanthine hydrochloride in a dose of 10 mgm. injected into the femoral artery of a dog produced dilation of the blood vessels in the leg and general hypotension. 

The neurotransmitter acetylcholine (ACh) exerts its diverse pharmacological actions via binding to and subsequent activation of two general classes of cell surface receptors, the nicotinic and the mAChRs. These two classes of ACh receptors have distinct structural and functional properties. The nicotinic receptors,... 

In the preceding sections we have outlined and evaluated the methods by which NT function may be studied and considered the general pharmacology of the major NTs. This should enable us to consider the possible role of NTs in disease states and drug action. 

Dopamine should generally be avoided in decompensated HF, but its pharmacologic actions may be preferable to dobutamine or milrinone in patients with marked systemic hypotension or cardiogenic shock in the face of elevated ventricular filling pressures, where dopamine in doses greater than 5 mcg/kg/min may be necessary to raise central aortic pressure. 

Having considered the general relationships of chemical structure with these four different pharmacological actions, might we first look in detail at six compounds whose clinical... 

Another challenge is how and when to consider isomers, metabolites, and the actual finished product. In general, any parent compound and its major metabolite(s) that achieve, or are suspected to achieve, systemic exposure in humans should be evaluated. Assessment of the effects of major (i.e., >25% of the parent) human-specific metabolite(s), if absent or present only at relatively low concentrations in animals, should be considered.25,52 This is of particular importance if the metabolite(s) is known to substantially contribute to the pharmacological actions of the NCE. In vitro or in vivo testing of the individual isomers should also be considered. Moreover, studies on the finished product are only necessary if the pharmacokinetics/pharmacodynamics is substantially altered in comparison to the active NCE tested previously. 

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