The pharmacology of prazosin, a novel antihypertensive agent

Cavero, Icilio; Roach, A. G.

doi:10.1016/0024-3205(80)90561-5

Cited by 156 publications

(53 citation statements)

References 78 publications

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“…A 30-min pretreatment time was used in our prior study and also in other studies (Blanc et al, 1994;Darracq et al, 1998). In addition, the 30-min pretreatment time is within the rise time of peak absorption with oral administration (Cavero and Roach, 1980). The dose of cocaine was selected because it is sufficient to induce sensitization of its locomotor activating effects and reinstate extinguished cocaine selfadministration behavior.…”

Section: Pre-exposurementioning

confidence: 99%

Previous Exposure to Cocaine Enhances Cocaine Self-Administration in an Alpha 1-Adrenergic Receptor Dependent Manner

Zhang

Kosten

2006

Neuropsychopharmacol

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Noradrenergic transmission is implicated in the biochemical and behavioral effects of cocaine. Recently, we demonstrated that the alpha 1-adrenergic receptor antagonist prazosin attenuates cocaine-induced reinstatement of drug-seeking behavior. We now assessed whether prazosin could counter the effect of previous exposure to cocaine to enhance subsequent self-administration behavior. Rats were pre-exposed to systemic injections of either saline, prazosin (0.3 mg/kg), saline + cocaine (10 mg/kg), or prazosin + cocaine for 5 days. Starting 15-18 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.5 mg/kg/infusion) under a fixed ratio 3 (FR3) schedule of reinforcement. Several tests were conducted. First, responding for cocaine under an FR3 schedule was assessed across several doses (0.125-1.0 mg/kg/infusion). Second, responding for cocaine (0.5 mg/kg/infusion) under a progressive-ratio (PR) schedule was examined for 6 consecutive days. Finally, responding for cocaine (0, 0.5, and 1.0 mg/kg/infusion) was determined under the PR schedule of reinforcement. Results showed that cocaine pre-exposed rats self-administer more cocaine compared to saline preexposed rats when tested under both the FR and PR schedules. Rats pre-exposed to cocaine plus prazosin did not show enhanced cocaine self-administration. These rats, as well those pre-exposed to prazosin alone, showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, previous exposure to cocaine enhanced cocaine self-administration, an effect that appears to involve activation of alpha 1-adrenergic receptors. These data, along with several recent studies, show further support for the contribution of noradrenergic transmission in the behavioral effects of cocaine. Neuropsychopharmacology (2007) 32, 638-645.

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Section: Pre-exposurementioning

confidence: 99%

Previous Exposure to Cocaine Enhances Cocaine Self-Administration in an Alpha 1-Adrenergic Receptor Dependent Manner

Zhang

Kosten

2006

Neuropsychopharmacol

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“…It is 10 times more potent, on a molar basis, than phentolamine, a mixed a1/a2-antagonist, in inhibiting the vasoconstrictive action of norepinephrine. When prazosin is administered in hypotensive doses, tachycardia and increased renin release are relatively infrequent, probably because of the absence of blocking activity against the presynaptic a-receptor and the combined action of the drug in reducing vascular tone in both resistance (arterioles) and capacitance (veins) beds (13,(18)(19)(20). there is little evidence to support a CNS site of action for prazosin and, consistent with a specific a1-adrenergic receptor effect, it does not have any demonstrable ganglionic, vagal, X3-blocking, or sympathetic neuronal-blocking properties (19,20).…”

Section: Discussionmentioning

confidence: 99%

Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat.

Brosnan¹,

Goldmuntz²,

Cammer³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Prazosin, an antagonist of a1-adrenergic receptors, has been found to suppress the clinical and histological expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Suppression was more significant in females than in males and was a dose-dependent phenomenon. Analysis of the effect of other adrenergic receptor antagonists supports the conclusion that the suppressive effect of prazosin is a consequence of blockade of the a,-receptor since treatment with either the a2-antagonist yohimbine or the P-antagonist propranolol exacerbated the disease, whereas treatment with the long-acting mixed al/a2-antagonist phenoxybenzamine had some suppressive activity. Treatment with prazosin was also able to suppress clinical and histological signs of EAE in animals sensitized by adoptive transfer with activated spleen or lymph node cells. Whether prazosin acts through altering vascular permeability or the immune response, or both, remains to be determined.

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“…The rabbit saphenous artery contracted well to exogenously applied noradrenaline. Prazosin, a selective postjunctional ac,-adrenoceptor antagonist (Cavero & Roach, 1980), significantly antagonized this response. On the other hand, contractions to electrical stimulations were only partially antagonized (b) pD2 values and mean slopes for the concentration-response curve to histamine in rabbit isolated saphenous artery at the start of the experiment and after the tissues have been treated with aj,-methylene ATP and prazosin.…”

Section: Effect Ofprazosin On Neurogenic Contractionsmentioning

confidence: 99%

A pharmacological study of the rabbit saphenous artery in vitro: a vessel with a large purinergic contractile response to sympathetic nerve stimulation

Burnstock

Warland

1987

British J Pharmacology

126

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1 Mechanical responses to transmural electrical stimulation were recorded in isolated transverse ring preparations of rabbit saphenous artery. Electrical stimulation for a period of 1 s produced a rapid monophasic contraction and, for a period of 1 min, a biphasic contraction consisting of a rapid constriction followed by a slower sustained constriction. All contractions were abolished in the presence of tetrodotoxin (1 glg ml-') or guanethidine (4 JiM).2 After desensitization of the P2-purinoceptor with aj-methylene ATP, contractions to electrical stimulation for 1 s were reduced significantly at all frequencies tested: responses evoked by stimulation at 4 Hz were usually almost completely inhibited, whereas those evoked by stimulation at 64 Hz were only partially inhibited. On the other hand, in the presence of the a-adrenoceptor antagonist, prazosin, neurogenic contractions were only partially reduced: at 4 Hz there was no significant reduction in the neurogenic contractions while at 32 and 64 Hz, contractions were reduced by an average of20 and 28% respectively. Usually all contractions were abolished by a combination of the two drugs. 3 Prazosin antagonized contractions of the vessel to exogenously applied noradrenaline but not to ATP, whereas desensitization of the P2-purinoceptor with a,-methylene ATP blocked responses to ATP but not those to noradrenaline. The concentration-response curve to histamine was not affected by treatment of the vessel with prazosin, or after desensitization of the P2-purinoceptor with ax,fmethylene ATP. 4 These results suggest that noradrenaline and ATP are co-released from sympathetic nerves supplying the rabbit saphenous artery, both substances being involved in the mechanical contractions of this tissue. Further, the ratio of ATP to noradrenaline involved in these mechanical contractions is dependent upon the frequency of stimulation, but at all frequencies tested the purinergic component is greater than the adrenergic component.

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The pharmacology of prazosin, a novel antihypertensive agent

Cited by 156 publications

References 78 publications

Previous Exposure to Cocaine Enhances Cocaine Self-Administration in an Alpha 1-Adrenergic Receptor Dependent Manner

Previous Exposure to Cocaine Enhances Cocaine Self-Administration in an Alpha 1-Adrenergic Receptor Dependent Manner

Prazosin, an alpha 1-adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat.

A pharmacological study of the rabbit saphenous artery in vitro: a vessel with a large purinergic contractile response to sympathetic nerve stimulation

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