摘要:

The pharmacotherapy of migraine has advanced in parallel with our understanding of the pathophysiology of the disease. It is likely that it is the gap in our knowledge of the pathogenesis as opposed to the pathophysiology of migraine which hinders development of preventative agents. This century has seen the shift from the vascular theory of migraine pathophysiology (i.e. that cranial vessels were the prime movers in the disorder and thus vasoconstriction would be the prime treatment) to a more integrated neurovascular theory. The neurovascular theory takes the view that vascular change is secondary to neural activation, so changes such as release of trigeminal neuropeptides is predicted, has been demonstrated and suggests a possible new treatment. Similarly, it may be possible to block trigeminal nociceptive transmission in the trigeminal nucleus which might avoid the vascular adverse effects that, while small, plague current treatments. The future for migraine and cluster headache, the neurovascular headaches, is bright as we unravel their biology and this leads to further therapeutic advances.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&DInsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Allergan is developing botulinum toxin type A (AGN 191622) as Botox®. Botulinum toxin A is a purified neurotoxin complex derived from the bacteriumClostridium botulinumwhich produces 7 neurotoxins which are structurally similar but immunologically distinct. Botox® is a purified 900kD complex, made up of a 150kD neurotoxin moiety, haemagglutinin and other non-toxic proteins.Botox® dose-dependently and reversibly inhibits hyperactive muscle contraction for ≥3 months. Allergan states that the action of the drug consists of a 3-step process of binding to peripheral cholinergic nerve endings, forming a toxin-containing vesicle by internalisation and then blocking acetylcholine release through the cleavage of the acetylcholine-releasing protein SNAP-25. Neuromuscular transmission is eventually re-established through the sprouting of new axon terminals.Botulinum toxin A is in phase II clinical trials in the US for the treatment of migraine. It has been launched in various countries for the treatment of blepharospasm, strabismus, spasmodic torticollis (cervical dystonia), and spasticity in juvenile cerebral palsy. The drug is also in development for the management of upper limb spasticity after stroke in adults (US and Europe), lower back pain (US), hemi-facial spasm (Japan), chronic anal fissures (Italy), chemical denervation of sweat glands (Europe), and the removal of brow furrows.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Dapitant (RPR 100893) is a selective nonpeptide perhydroisoindolone derivative with antagonist activity at neurokinin (NK)1 receptors. NK1 receptors are thought to mediate the neurogenic inflammatory effects of substance P. The related compound, RP 67580, is also a selective substance P antagonist and has been shown to block neurogenic extravasation in the dura mater after electrical or chemical trigeminal stimulation.Dapitant has shown promise as an antimigraine agent in several animal models, with >100-fold higher potency than sumatriptan, dihydroergotamine or aspirin (acetylsalicylic acid) with respect to inhibition of dural neurogenic inflammation. Dapitant is currently in phase II clinical trials with Rhône-Poulenc Rorer in France as an oral therapy for migraine and pain.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Gabapentin (CI 945, GOE 3450) is a novel anticonvulsant agent that was developed by Warner-Lambert for the treatment of epilepsy.Gabapentin has therapeutic efficacy as adjunctive therapy in patients with complex partial epilepsy and secondarily generalised epilepsy resistant to conventional treatment. High-dose monotherapy with gabapentin also appears to be beneficial and well tolerated in patients with treatment-resistant and newly diagnosed partial seizures. The efficacy and tolerability profile of gabapentin, coupled with its favourable pharmacokinetic properties and lack of drug interactions, indicate that this drug is a useful addition to anticonvulsant polytherapy. A possibly undesirable characteristic of gabapentin is the requirement for 3 times daily administration.The mechanism of action of gabapentin is not fully understood, although it does not appear to be similar to that of conventional anticonvulsant agents. Gabapentin is a structural analogue of the neurotransmitter &ggr;-aminobutyric acid (GABA). Nevertheless, the anticonvulsant activity of gabapentin appears to be distinct from its GABA-related effects.Clinical studies are underway in patients with migraine. Gabapentin has also been found to ease neuropathic pain, and is currently undergoing clinical trials in patients with painful diabetic neuropathies. Gabapentin is also being investigated for use in patients with phantom limb pain.Gabapentin was being investigated in the US for amyotrophic lateral sclerosis, but results a 9-month, placebo-controlled phase III trial has failed to find any benefits for gabapentin over placebo. Warner-Lambert has no plans to continue with further trials of gabapentin in patients with amyotrophic lateral sclerosis. Clinical trials in this indication have also been conducted by Italian researchers. A clinical study of gabapentin in the treatment of patients with spinal muscular atrophy, a disease of the motor neurons, has been initiated in Canada and the US.Marketing rights for Japan, Korea and Taiwan are held by Fujisawa.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;IS 159, a serotonin 5-HT1 receptor agonist, has been undergoing phase II development with Immunotech in France as an intranasal formulation for the treatment of migraine. The Medicines Company has acquired exclusive worldwide rights to IS 159 for late-stage development and commercialisation, and has initiated phase II trials in theUS. TheMedicines Company plans to initiate further European trials of IS 159 in the near future.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

S-fluoxetine, developed by the US chiral drug company Sepracor, is the single isomer formulation of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine (Prozac®; Eli Lilly). The efficacy of S-fluoxetine in migraine prophylaxis is currently being investigated in phase II trials in the US and the UK. The company predicts that S-fluoxetine could reach the market by the year 2000.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Vigabatrin (&ggr;-vinyl-GABA, GVG, MDL 71754, RMI 71754), a close structural analogue of &ggr;-aminobutyric acid (GABA), acts as a potent, enzyme-activated irreversible inhibitor of GABAaminotransferase. Vigabatrin crosses the blood-brain barrier and dose-dependently increases levels of GABA in the brain. It was developed by Hoechst Marion Roussel for the treatment of epilepsy.Vigabatrin is effective in treating adults and children with partial and secondarily generalised tonic clonic seizures when used adjunctively. Vigabatrin is well tolerated, but increased risk of concentric visual field defects is now emerging. Such an adverse event is thus far unique and specific to vigabatrin. It has been suggested that until the issue of visual field defectswith vigabatrin has been properly investigated, other anticonvulsants should be considered before vigabatrin, with the possible exception of infantile spasms.Vigabatrin has been effective in the treatment of patientswith previously drugresistant migraine. It also may have potential as a treatment for nicotine and cocaine addiction according to research being funded by the National Institute on Drug Abuse in the US. Clinical studies in this indication are being planned for North America and Canada.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Zatosetron (LY 277359, LY 19167) is a serotonin 5-HT3 receptor antagonist undergoing phase III clinical trials with Eli Lilly in theUS for treatment of chronic anxiety. Phase II trials in Japan have been discontinued. Zatosetron has also shown promise as an antiemetic agent and is undergoing phase II trials in the US for this indication. AUS phase II clinical trial of zatosetron failed to demonstrate significant improvement in patients with migraine when the drug was administered as a single IV infusion.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&DInsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS